Author: "Catheline, Vilain" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Catheline, Vilain"' showing total 85 results

Start Over Author "Catheline, Vilain"

85 results on '"Catheline, Vilain"'

1. Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhageResearch in context

Author: Sarah McNeilly, Cameron R. Thomson, Laura Gonzalez-Trueba, Yuan Yan Sin, Alessandra Granata, Graham Hamilton, Michelle Lee, Erin Boland, John D. McClure, Cristina Lumbreras-Perales, Alisha Aman, Apoorva A. Kumar, Marco Cantini, Caglar Gök, Delyth Graham, Yasuko Tomono, Christopher D. Anderson, Yinhui Lu, Colin Smith, Hugh S. Markus, Marc Abramowicz, Catheline Vilain, Rustam Al-Shahi Salman, Manuel Salmeron-Sanchez, Atticus H. Hainsworth, William Fuller, Karl E. Kadler, Neil J. Bulleid, and Tom Van Agtmael
Subjects: Collagen, Basement membrane, Cerebrovascular disease, Stroke, Small vessel disease, Endothelial dysfunction, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure. Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH. Findings: Col4a1 missense mutations cause early-onset CSVD independent of hypertension, with enhanced vasodilation of small arteries due to endothelial dysfunction, vascular wall thickening and reduced stiffness. Mechanistically, the early-onset dysregulated endothelium-dependent hyperpolarization (EDH) is due to reduced collagen IV levels with elevated activity and levels of endothelial Ca2+-sensitive K+ channels. This results in vasodilation via the Na/K pump in vascular smooth muscle cells. Our data support this endothelial dysfunction preceding development of CSVD-associated ICH is due to increased cytoplasmic Ca2+ levels in endothelial cells. Moreover, cerebral blood vessels of patients with sporadic CSVD show genotype-dependent mechanisms with wall thickening and lower collagen IV levels in those harboring common non-coding COL4A1/COL4A2 risk alleles. Interpretation: COL4A1/COL4A2 variants act in genetic and sporadic CSVD with ICH via dysregulated EDH, and altered vascular wall thickness and biomechanics due to lower collagen IV levels and/or mutant collagen IV secretion. These data highlight EDH and collagen IV levels as potential treatment targets. Funding: MRC, Wellcome Trust, BHF.
Published: 2024
Full Text: View/download PDF

2. Carbamazepine efficacy in a severe electro‐clinical presentation of SLC13A5‐epilepsy

Author: Roberto Santalucia, Catheline Vilain, Julie Soblet, Corinne De Laet, Aline Vuckovic, Jörg König, and Alec Aeby
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Recessive mutations in the SLC13A5 gene encoding the sodium‐dependent citrate transporter are a recently identified cause of developmental and epileptic encephalopathy. Here, we describe a child harboring a novel homozygous loss‐of‐function mutation in the SLC13A5 gene (c.1496C>T–p.Ser499Phe) and exhibiting an unusual extremely severe neonatal presentation with drug‐resistant seizures and burst‐suppression EEG pattern. Early carbamazepine use resulted in dramatic improvement both clinically and on EEG features. Follow‐up from the neonatal period to the age of 4 years is documented. This case expands the electro‐clinical phenotype associated with SLC13A5‐related disease and confirms the efficacy and safety of carbamazepine in nonstructural early‐onset epilepsies.
Published: 2022
Full Text: View/download PDF

3. An exome-wide study of renal operational tolerance

Author: Annick Massart, Richard Danger, Catharina Olsen, Mary J. Emond, Ondrej Viklicky, Valérie Jacquemin, Julie Soblet, Sarah Duerinckx, Didier Croes, Camille Perazzolo, Petra Hruba, Dorien Daneels, Ben Caljon, Mehmet Sukru Sever, Julio Pascual, Marius Miglinas, the Renal Tolerance Investigators, Isabelle Pirson, Lidia Ghisdal, Guillaume Smits, Magali Giral, Daniel Abramowicz, Marc Abramowicz, Sophie Brouard, Maria Aguilar Rodríguez, Friederike Bachmann, Rajendra Bahadur Shahi, Frederike Bemelman, Luboslav Bena, Luigi Biancone, Laura Braun, Klemens Budde, Alejandro Camargo-Salamanca, Katia Clemente, Hulya Colak, Adrian Covic, Jacques Degreve, Philippe Gatault, François Glowacki, Karine Hadaya, Marc Hazzan, Bénédicte Janbon, Christophe Legendre, Umberto Maggiore, Anja Mühlfeld, Maarten Naesens, Christian Noël, Rainer Oberbauer, Evangeline Pillebout, Gian Benedetto Piredda, Francesco Pisani, Ana Ramírez Puga, Tomas Reischig, Francisco González-Roncero, Søren Schwartz Sørensen, Daniel Seron Micas, Nurhan Seyahi, Dimitrie Siriopol, Goce Spasovski, Jean-François Subra, Erik Teugels, Serhan Tuǧlular, Sonia Van Dooren, Catheline Vilain, Florence Villemain, Xavier Warling, Bruno Watschinger, and Laurent Weekers
Subjects: exome sequencing, renal transplantation, operational tolerance, NGAL, LCN2, Homer2, Medicine (General), R5-920
Abstract: BackgroundRenal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients.MethodsWe set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 transplant recipients who maintained good allograft function without immunosuppression for at least 1 year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.ResultsWe identified rare variants of HOMER2 (3/36, FDR 0.0387), IQCH (5/36, FDR 0.0362), and LCN2 (3/36, FDR 0.102) in 10 tolerant patients vs. 0 controls. One patient carried a variant in both HOMER2 and LCN2. Furthermore, the three genes showed an identical variant in two patients each. The three genes are expressed at the primary cilium, a key structure in immune responses.ConclusionRare protein coding variants are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.ClinicalTrials.gov, identifier: NCT05124444.
Published: 2023
Full Text: View/download PDF

4. Acquired Zinc Deficiency Mimicking Acrodermatitis Enteropathica in a Breast-Fed Premature Infant

Author: Giovanna D’Amico, Corinne De Laet, Guillaume Smits, Deborah Salik, Guillaume Deprez, Catheline Vilain, Pascale Perlot, and Alfredo Vicinanza
Subjects: zinc deficiency, acrodermatitis enteropathica, premature infant, breastfeeding, zinc supplementation, Medicine, Pediatrics, RJ1-570
Abstract: We present a case of a transient acquired zinc deficiency in a breast-fed, 4-month-old-male prematurely born infant, with acrodermatitis enteropathica-like symptoms such as crusted, eroded, erythemato-squamous eruption in periorificial and acral patterns. The laboratory investigations showed low zinc levels in the infant’s and the mother’s serum and in the mother’s milk; genetic analysis did not show any mutation in the SLC39A4 gene, involved in acrodermatitis enteropathica. Acquired zinc deficiency is often found in premature infants because of their increased requirement, the low serum and milk zinc levels in breastfeeding women being also an important risk factor, as in this case. A prompt zinc supplementation is essential for the good prognosis of the disease.
Published: 2021
Full Text: View/download PDF

5. Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations

Author: Pascal Brouillard, Matthieu J. Schlögel, Nassim Homayun Sepehr, Raphaël Helaers, Angela Queisser, Elodie Fastré, Simon Boutry, Sandra Schmitz, Philippe Clapuyt, Frank Hammer, Anne Dompmartin, Annamaria Weitz-Tuoretmaa, Jussi Laranne, Louise Pasquesoone, Catheline Vilain, Laurence M. Boon, and Miikka Vikkula
Subjects: Lymphatic malformation, Isolated, Gene, Mutation, Somatic, PI3K, Medicine
Abstract: Abstract Background Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients’ genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)]. Results We identified a somatic PIK3CA mutation in resected lesions of 108 out of 143 patients (75.5%). The frequency of the variant allele ranged from 0.54 to 25.33% in tissues, and up to 47% in isolated endothelial cells. We detected a statistically significant difference in the distribution of mutations between patients with common and combined LM compared to the syndromes, but not with KTS. Moreover, the variant allele frequency was higher in the syndromes. Conclusions Most patients with an common or combined lymphatic malformation with or without overgrowth harbour a somatic PIK3CA mutation. However, in about a quarter of patients, no such mutation was detected, suggesting the existence of (an)other cause(s). We detected a hotspot mutation more frequently in common and combined LMs compared to syndromic cases (CLOVES and PROS). Diagnostic genotyping should thus not be limited to PIK3CA hotspot mutations. Moreover, the higher mutant allele frequency in syndromes suggests a wider distribution in patients’ tissues, facilitating detection. Clinical trials have demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. Genotyping might lead to an increase in efficacy, as treatments could be more targeted, and responses could vary depending on presence and type of PIK3CA-mutation.
Published: 2021
Full Text: View/download PDF

6. A prenatal case of lissencephaly with cerebellar hypoplasia: New mutation in RELN gene

Author: Claire Balza, Giulia Garofalo, Teresa Cos, Julie Désir, Xin Kang, Kathelijn Keymolen, Julie Soblet, Kim Van Berkel, Catheline Vilain, Wafa Ben Abbou, and Marie Cassart
Subjects: cerebellar hypoplasia, lissencephaly, reelinopathy, RELN, Medicine, Medicine (General), R5-920
Abstract: Abstract Reelinopathies cause a distinctive lissencephaly type associated with cerebellar hypoplasia. To help further management, we wanted to report here the first prenatal diagnosis due to a homozygous inherited reelinopathy.
Published: 2021
Full Text: View/download PDF

7. The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?

Author: Fiorenza Ulgiati, Sophie Lhoir, Irina Balikova, Sylvie Tenoutasse, Emese Boros, Catheline Vilain, Claudine Heinrichs, and Cécile Brachet
Subjects: AAAS, ALADIN, Triple A syndrome, OCT, retina, neurodegeneration, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ObjectiveExperimental evidence suggests that the clinical manifestations of Triple A syndrome result from oxidative stress. Several conditions caused by oxidative stress display retinal involvement. Our objective was to assess the retina and optic nerve involvement in children with Triple A syndrome.MethodsEleven patients with genetically proven Triple A syndrome followed-up in our centre were approached for study participation. The main outcome was the measurement of the thicknesses of the different retinal layers by Optical Coherence Tomography (OCT).Results9 patients with triple A syndrome had OCT measurements. 7 patients were children and 2 were adults; 4 were females and 5 were males. The 7 paediatric patients had at least two OCT measured at a mean interval of 7.9 months after the first one. The average Retinal Nerve Fibre Layer thickness was 74 ± 10 µm in patients compared to the paediatric reference range of 100 ± 2 µm (p
Published: 2021
Full Text: View/download PDF

8. Phenotypes and genotypes in non‐consanguineous and consanguineous primary microcephaly: High incidence of epilepsy

Author: Sarah Duerinckx, Julie Désir, Camille Perazzolo, Cindy Badoer, Valérie Jacquemin, Julie Soblet, Isabelle Maystadt, Yusuf Tunca, Bettina Blaumeiser, Berten Ceulemans, Winnie Courtens, François‐Guillaume Debray, Anne Destree, Koenraad Devriendt, Anna Jansen, Kathelijn Keymolen, Damien Lederer, Bart Loeys, Marije Meuwissen, Stéphanie Moortgat, Geert Mortier, Marie‐Cécile Nassogne, Tayeb Sekhara, Rudy Van Coster, Jenny Van Den Ende, Nathalie Van der Aa, Hilde Van Esch, Olivier Vanakker, Helene Verhelst, Catheline Vilain, Sarah Weckhuysen, Sandrine Passemard, Alain Verloes, Alec Aeby, Nicolas Deconinck, Patrick Van Bogaert, Isabelle Pirson, and Marc Abramowicz
Subjects: brain developmental disorders, consanguinity, epilepsy, Mendeliome, primary microcephaly, rare disease, Genetics, QH426-470
Abstract: Abstract Background Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results Pathogenic variants in ASPM and WDR62 were the most frequent causes in non‐consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non‐consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients.
Published: 2021
Full Text: View/download PDF

9. A pathogenic CTBP1 variant featuring HADDTS with dystrophic myopathology

Author: Hazim Kadhim, Eliane El-Howayek, Sandra Coppens, Jennifer Duff, Ana Topf, Jean-Paul Kaleeta, Paolo Simoni, Grammatina Boitsios, Gauthier Remiche, Volker Straub, Catheline Vilain, and Nicolas Deconinck
Subjects: Neurology, Pediatrics, Perinatology and Child Health, Neurology (clinical), Genetics (clinical)
Published: 2023

10. Co-Occurrence of Hypohidrotic Ectodermal Dysplasia and Food Protein-Induced Enterocolitis Syndrome: A Report of a New Ectodysplasin A Variant

Author: Déborah Salik, Florine Moulart, Martina Marangoni, Dimitrios Salamouras, Marie-Sophie André, and Catheline Vilain
Subjects: Dermatology
Abstract: Introduction: Ectodermal dysplasias (EDs) are a large group of rare and complex genetic disorders, affecting the development of two or more ectodermal structures. Hypohidrotic ED (HED) is the most frequent ED’s phenotype and is characterized by hypodontia, hypotrichosis, and hypo/anhidrosis, leading to heat intolerance and hyperthermia. Case Presentation: We report a case of a 2-year-old girl with hair and teeth abnormalities associated with severe digestive symptoms responsible for failure to thrive. Genetic analysis by mass sequencing in parallel on a 4,867-gene panel was performed in duo (index case and her mother). The girl showed the presence of a new de novo c.100dupG variant in EDA responsible for HED associated with a diagnosis of food protein-induced enterocolitis syndrome (FPIES). Conclusion: We describe a patient with HED and a new EDA variant associated with a diagnosis of FPIES, both implicating increased intestinal permeability. The inclusion of FPIES as a possible digestive symptom of HED can be suggested, although it may occur only in a context of atopy.
Published: 2022

11. Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability

Author: Claudio Reggiani, Sandra Coppens, Tayeb Sekhara, Ivan Dimov, Bruno Pichon, Nicolas Lufin, Marie-Claude Addor, Elga Fabia Belligni, Maria Cristina Digilio, Flavio Faletra, Giovanni Battista Ferrero, Marion Gerard, Bertrand Isidor, Shelagh Joss, Florence Niel-Bütschi, Maria Dolores Perrone, Florence Petit, Alessandra Renieri, Serge Romana, Alexandra Topa, Joris Robert Vermeesch, Tom Lenaerts, Georges Casimir, Marc Abramowicz, Gianluca Bontempi, Catheline Vilain, Nicolas Deconinck, and Guillaume Smits
Subjects: Functional genomics, Promoters, Neurodevelopmental disorders, Intellectual disability, DLG2, Medicine, Genetics, QH426-470
Abstract: Abstract Background Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders. Methods Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play. Results Integrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients’ clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories. Conclusions While protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases.
Published: 2017
Full Text: View/download PDF

12. Evaluation of neurodevelopmental symptoms in 10 cases of neonatal ichthyosis and sclerosing cholangitis syndrome

Author: Deborah Salik, Smail Hadj‐Rabia, Daniel Hohl, Hassan Vahidnezhad, Leila Youssefian, Adèle Rakosi, Chantal Dangoisse, Martina Marangoni, Catheline Vilain, and Guillaume Smits
Subjects: Pediatrics, Perinatology and Child Health, Dermatology
Published: 2022

13. <scp>Ehlers‐Danlos</scp> /myopathy overlap syndrome caused by a large de novo deletion in <scp> COL12A1 </scp>

Author: Sandra Coppens, Laurence Desmyter, Manuel Koch, Semra Özcelik, Emily O'Heir, Patrick Van Bogaert, Catheline Vilain, and Florence Christiaens
Subjects: Genetics, Genetics (clinical)
Published: 2022

14. A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases in extracellular matrix abnormalities

Author: Maha Al-Thani, Mary Goodwin-Trotman, Steven Bell, Krushangi Patel, Lauren K Fleming, Catheline Vilain, Marc Abramowicz, Stuart M Allan, Tao Wang, Zameel Cader, Karen Horsburgh, Tom Van Agtmael, Sanjay Sinha, Hugh S Markus, and Alessandra Granata
Abstract: /SummaryCerebral small vessel disease (SVD) affects the small vessels in the brain and is a leading cause of stroke and dementia. Emerging evidence supports a role of the extracellular matrix (ECM), at the interface between blood and brain, in the progression of SVD pathology but this remains poorly characterized.To address ECM role in SVD, we developed a co-culture model of mural and endothelial cells using human induced pluripotent stem cells from patients withCOL4A1/A2SVD-related mutations. This model revealed that these mutations induce apoptosis, migration defects, ECM remodelling and transcriptome changes in mural cells. Importantly, these mural cell defects exert a detrimental effect on endothelial cells tight junctions through paracrine actions.COL4A1/A2models also express high levels of matrix metalloproteinases (MMP) and inhibiting MMP activity partially rescues the ECM abnormalities and mural cell phenotypic changes. These data provide a basis for targeting MMP as a therapeutic opportunity in SVD.HighlightsA novel human iPSC-derived model of genetic SVD due to collagen IV (COL4A1/A2) mutations is describedMural cells expressingCOL4A1/A2mutations have prominent ECM abnormalities as seen in patients and mouse models and contribute to endothelial cells defectsECM and endothelial cells abnormalities can be rescued by MMP inhibition in theCOL4A1/A2model
Published: 2023

15. Biallelic gephyrin variants lead to impaired GABAergic inhibition in a patient with developmental and epileptic encephalopathy

Author: Arthur Macha, Florian Hetsch, Patrick Van Bogaert, Borislav Dejanovic, Steffen Fricke, Franziska Neuser, Jose Angel Santamaria-Araujo, Vanessa Kress, Filip Liebsch, Lena Johannes, Alec Aeby, Catheline Vilain, Sarah Weckhuysen, Guenter Schwarz, Tania Djémié, and Jochen C. Meier
Subjects: Scaffold protein, Biology, Inhibitory postsynaptic potential, Epilepsy, Postsynaptic potential, Genetics, medicine, Humans, Missense mutation, Receptor, Molecular Biology, Genetics (clinical), Brain Diseases, Gephyrin, Membrane Proteins, General Medicine, Receptors, GABA-A, medicine.disease, Cell biology, Chemistry, Synapses, biology.protein, Human medicine, Receptor clustering, Carrier Proteins
Abstract: Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition is linked to epilepsy. Gephyrin (Geph) is the principal scaffolding protein at inhibitory synapses and is essential for postsynaptic clustering of glycine (GlyRs) and GABA type A receptors. Consequently, gephyrin is crucial for maintaining the relationship between excitation and inhibition in normal brain function and mutations in the gephyrin gene (GPHN) are associated with neurodevelopmental disorders and epilepsy. We identified bi-allelic variants in the GPHN gene, namely the missense mutation c.1264G > A and splice acceptor variant c.1315-2A > G, in a patient with developmental and epileptic encephalopathy. We demonstrate that the splice acceptor variant leads to nonsense-mediated mRNA decay. Furthermore, the missense variant (D422N) alters gephyrin structure, as examined by analytical size exclusion chromatography and circular dichroism-spectroscopy, thus leading to reduced receptor clustering and sensitivity towards calpain-mediated cleavage. In addition, both alterations contribute to an observed reduction of inhibitory signal transmission in neurons, which likely contributes to the pathological encephalopathy.
Published: 2021

16. Acquired Zinc Deficiency Mimicking Acrodermatitis Enteropathica in a Breast-Fed Premature Infant

Author: Guillaume Smits, Alfredo Vicinanza, Corinne De Laet, Pascale Perlot, Guillaume Deprez, Déborah Salik, Catheline Vilain, and Giovanna D’Amico
Subjects: 0301 basic medicine, breastfeeding, acrodermatitis enteropathica, Breastfeeding, Physiology, chemistry.chemical_element, Case Report, Zinc, Disease, Pediatrics, RJ1-570, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, zinc deficiency, Medicine, Risk factor, 030109 nutrition & dietetics, business.industry, Acrodermatitis, Acrodermatitis enteropathica, zinc supplementation, medicine.disease, premature infant, chemistry, Zinc deficiency, business
Abstract: We present a case of a transient acquired zinc deficiency in a breast-fed, 4-month-old-male prematurely born infant, with acrodermatitis enteropathica-like symptoms such as crusted, eroded, erythemato-squamous eruption in periorificial and acral patterns. The laboratory investigations showed low zinc levels in the infant’s and the mother’s serum and in the mother’s milk; genetic analysis did not show any mutation in the SLC39A4 gene, involved in acrodermatitis enteropathica. Acquired zinc deficiency is often found in premature infants because of their increased requirement, the low serum and milk zinc levels in breastfeeding women being also an important risk factor, as in this case. A prompt zinc supplementation is essential for the good prognosis of the disease.
Published: 2021

17. First Report on Fetal Cerebral Polyglucosan Bodies in Mucopolysaccharidosis Type VII

Author: Hazim Kadhim, Valérie Segers, Catheline Vilain, Julie Désir, and Nicky D’Haene
Subjects: Pediatrics, RJ1-570
Abstract: We report on the detection of discordant inclusions in the brain of a 25-week female fetus with a very rare lysosomal storage disease, namely, Sly disease (mucopolysaccharidosis (MPS) type VII), presenting with nonimmune hydrops fetalis. Besides vacuolated neurons, we found abundant deposition of polyglucosan bodies (PGBs) in the developing brain of this fetus in whom MPS-VII was corroborated by lysosomal beta-glucuronidase-deficiency detected in fetal blood and fetal skin-fibroblasts and by the presence of a heterozygous pathogenic variant in the GUSB gene in the mother. Fetal/neonatal metabolic disorders with PGB-deposition are extremely rare (particularly in relation to CNS involvement) and include almost exclusively subtypes of glycogenosis (types IV and VII). The accumulation of PGBs (particularly in the fetal brain) has so far not been depicted in Sly disease. This is the first report on such “aberrant” association. Besides, the detection of these CNS inclusions at such an early developmental stage is remarkably unique.
Published: 2017
Full Text: View/download PDF

18. A form of muscular dystrophy associated with pathogenic variants in JAG2

Author: Marie Rivera-Zengotita, Alison M. Barnard, Sanna Puusepp, Anna Łusakowska, Ros Quinlivan, Margherita Milone, Isabelle Draper, Katherine R. Chao, Erica L. Macke, Mait Nigul, Teepu Siddique, Vijay S. Ganesh, Sander Pajusalu, Nicolas Deconinck, Sanna Gudmundsson, Masashi Ogasawara, Sandra Donkervoort, Christine C. Bruels, Glenn A. Walter, Ehsan Ghayoor Karimiani, Christina A. Pacak, Reza Maroofian, Sabine Costagliola, Julia K. Goodrich, Anne H. O’Donnell-Luria, Mehran Beiraghi Toosi, Sandra Coppens, Yao Meng, Lynn Pais, Henry Houlden, Eleina M. England, Rasha El Sherif, Anne Boland-Auge, Bertold Schrank, Volker Straub, Gisèle Bonne, Catheline Vilain, Payam Mohassel, Tanya Stojkovic, Isabelle Nelson, Ichizo Nishino, Stefan Nicolau, Anna Kostera-Pruszczyk, Ben Weisburd, Jean-François Deleuze, Enzo Cohen, Michael G. Hanna, Hazim Kadhim, Peter B. Kang, Dorianmarie Vargas-Franco, Penny A. Handford, Katrin Õunap, Pilvi Ilves, Ana Töpf, Carsten G. Bönnemann, Brendan C. Lanpher, Eric W. Klee, and Andreas Hahn
Subjects: Male, Models, Molecular, 0301 basic medicine, Muscular Dystrophies, Myoblasts, Mice, 0302 clinical medicine, Drosophila Proteins, Muscular dystrophy, Child, Genetics (clinical), Genetics, Receptors, Notch, Myogenesis, Muscles, Middle Aged, Pedigree, Drosophila melanogaster, Phenotype, medicine.anatomical_structure, Glucosyltransferases, Child, Preschool, Female, Jagged-2 Protein, medicine.symptom, Signal Transduction, Adult, JAG2, JAG1, Adolescent, Notch signaling pathway, Biology, Article, Cell Line, Frameshift mutation, Young Adult, 03 medical and health sciences, Exome Sequencing, medicine, Animals, Humans, Amino Acid Sequence, Correction, Membrane Proteins, Muscle weakness, Skeletal muscle, medicine.disease, Human genetics, 030104 developmental biology, Haplotypes, Jagged-1 Protein, 030217 neurology & neurosurgery
Abstract: JAG2 encodes the Notch ligand Jagged2. The conserved Notch signaling pathway contributes to the development and homeostasis of multiple tissues, including skeletal muscle. We studied an international cohort of 23 individuals with genetically unsolved muscular dystrophy from 13 unrelated families. Whole-exome sequencing identified rare homozygous or compound heterozygous JAG2 variants in all 13 families. The identified bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy. Transcriptome analysis of muscle tissue from two participants suggested misregulation of genes involved in myogenesis, including PAX7. In complementary studies, Jag2 downregulation in murine myoblasts led to downregulation of multiple components of the Notch pathway, including Megf10. Investigations in Drosophila suggested an interaction between Serrate and Drpr, the fly orthologs of JAG1/JAG2 and MEGF10, respectively. In silico analysis predicted that many Jagged2 missense variants are associated with structural changes and protein misfolding. In summary, we describe a muscular dystrophy associated with pathogenic variants in JAG2 and evidence suggests a disease mechanism related to Notch pathway dysfunction.
Published: 2021

19. Two siblings with Bosch-Boonstra-Schaaf optic atrophy syndrome due to parental gonadal mosaicism

Author: Victoria van Renterghem, Catheline Vilain, Koenraad Devriendt, Ingele Casteels, Guillaume Smits, Julie Soblet, and Irina Balikova
Subjects: Genetics, General Medicine, Genetics (clinical)
Published: 2023

20. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Author: Lovric, Svjetlana, Goncalves, Sara, Gee, Heon Yung, Oskouian, Babak, Srinivas, Honnappa, Choi, Won-Il, Shril, Shirlee, Ashraf, Shazia, Tan, Weizhen, Rao, Jia, Airik, Merlin, Schapiro, David, Braun, Daniela A., Sadowski, Carolin E., Widmeier, Eugen, Jobst-Schwan, Tilman, Schmidt, Johanna Magdalena, Girik, Vladimir, Capitani, Guido, Suh, Jung H., Lachaussée, Noëlle, Arrondel, Christelle, Patat, Julie, Gribouval, Olivier, Furlano, Monica, Boyer, Olivia, Schmitt, Alain, Vuiblet, Vincent, Hashmi, Seema, Wilcken, Rainer, Bernier, Francois P., Innes, A. Micheil, Parboosingh, Jillian S., Lamont, Ryan E., Midgley, Julian P., Wright, Nicola, Majewski, Jacek, Zenker, Martin, Schaefer, Franz, Kuss, Navina, Greil, Johann, Giese, Thomas, Schwarz, Klaus, Catheline, Vilain, Schanze, Denny, Franke, Ingolf, Sznajer, Yves, Truant, Anne S., Adams, Brigitte, Désir, Julie, Biemann, Ronald, Pei, York, Ars, Elisabet, Lloberas, Nuria, Madrid, Alvaro, Dharnidharka, Vikas R., Connolly, Anne M., Willing, Marcia C., Cooper, Megan A., Lifton, Richard P., Simons, Matias, Riezman, Howard, Antignac, Corinne, Saba, Julie D., and Hildebrandt, Friedhelm
Published: 2017
Full Text: View/download PDF

21. Homozygous p.R31H GNRH1 mutation and normosmic congenital hypogonadotropic hypogonadism in a patient and self-limited delayed puberty in his relatives

Author: Claudine Heinrichs, Cécile Brachet, Julie Soblet, Caroline Gernay, Emese Boros, and Catheline Vilain
Subjects: 0301 basic medicine, Delayed puberty, Mutation, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Gonadotropin-releasing hormone, medicine.disease_cause, Asymptomatic, Frameshift mutation, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Congenital Hypogonadotropic Hypogonadism, medicine.symptom, business, Index case, Hormone
Abstract: Objectives Congenital hypogonadotropic hypogonadism (CHH) is a rare condition resulting from GnRH deficiency. Gonadotropin Releasing Hormone 1 (GNRH1) homozygous mutations are an extremely rare cause of normosmic CHH (nCHH). Most heterozygous individuals are asymptomatic, with the notable exception of individuals heterozygous for a p.R31C GNRH1 mutation. Case presentation The patient is an index case from a consanguineous family, presenting with severe CHH and his parents presenting with late puberty and normal fertility. The index case is homozygous for a p.R31H GNRH1 variant, both parents being heterozygous. The analysis of a panel of genes implicated in CHH does not show any other clinically relevant variant in any other gene tested. Conclusions GNRH1 mutations are a rare cause of nCHH. Five different mutations have been reported so far in homozygous individuals. Most are frameshift in nature but the one reported here causes an amino acid change in the Gonadotropin-releasing hormone (GnRH) decapeptide. Both independently reported patients with the p.R31H mutation are from Turkish origin. The question of the possible role of this mutation in the late puberty of the heterozygous parents needs further documentation. An analogy is made with the heterozygous individuals carrying the p.R31C and displaying partial CHH. No nonreproductive disorder is noted.
Published: 2020

22. Novel homozygous variant of carbonic anhydrase 8 gene expanding the phenotype of cerebellar ataxia, mental retardation, and disequilibrium syndrome subtype 3

Author: Wyatt W. Yue, Julie Soblet, Serge Goldman, Guillaume Smits, Alec Aeby, Lionel Paternoster, Sandra Coppens, Xavier De Tiège, Catheline Vilain, and Nicolas Deconinck
Subjects: 0301 basic medicine, Proband, Pathology, medicine.medical_specialty, Cerebellum, Cerebellar ataxia, business.industry, Sciences bio-médicales et agricoles, 030105 genetics & heredity, Phenotype, Temporal lobe, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Genetics, Brain positron emission tomography, Medicine, Ataxic Gait, medicine.symptom, business, Exome, Genetics (clinical)
Abstract: We report the case of an 11-year-old Syrian girl born to consanguineous parents, who presents an ataxic gait from early childhood. On clinical examination, she presented a severe static - kinetic cerebellar syndrome, walking without support is possible for short distances only. Strikingly, three consecutive MRIs did not show any sign of cerebellar abnormalities, but a brain positron emission tomography (PET) using [18F]-fluorodeoxyglucose (FDG) demonstrated a clear decrease in glucose metabolism in the cerebellum as well as the anterior and medial temporal lobe bilaterally. A clinical exome analysis identified a novel homozygous c.251A > G (p.Asn84Ser) likely pathogenic variant in the carbonic anhydrase 8 (CA8) gene. CA8 mutations cause cerebellar ataxia, mental retardation, and disequilibrium syndrome subtype 3 (CAMRQ3), a rare genetically autosomal recessive disorder, only described in four families, so far with the frequent observation of quadrupedal gait. The proband differed with other reported CA8 mutations by the absence of clear cerebellar signs on brain MRI and the presence of focal seizures. This report expands the clinical spectrum associated with mutations in CA8 and illustrates the possible discrepancy between (mild) neuro-radiological images (MRI) and (severe) clinical phenotype in young individuals. In contrast, the observation of clear cerebellar abnormal metabolic findings suggests that the FDG-PET scan may be used as an early marker for hereditary ataxia.
Published: 2020

23. Cancer risk and tumour spectrum in 172 patients with a germline

Author: Léa, Guerrini-Rousseau, Julien, Masliah-Planchon, Sebastian M, Waszak, Pia, Alhopuro, Patrick R, Benusiglio, Franck, Bourdeaut, Ines B, Brecht, Giada, Del Baldo, Sandeep Kumar, Dhanda, Maria Luisa, Garrè, Corrie E M, Gidding, Steffen, Hirsch, Pauline, Hoarau, Mette, Jorgensen, Christian, Kratz, Lucie, Lafay-Cousin, Angela, Mastronuzzi, Lorenza, Pastorino, Stefan M, Pfister, Christopher, Schroeder, Miriam Jane, Smith, Pia, Vahteristo, Roseline, Vibert, Catheline, Vilain, Nicolas, Waespe, Ingrid M, Winship, D Gareth, Evans, and Laurence, Brugieres
Abstract: Little is known about risks associated with germlineTo study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germlineOverall, 117/172 (68%)Germline
Published: 2022

24. Implementation of fetal clinical exome sequencing : comparing prospective and retrospective cohorts

Author: Caroline Gounongbe, An Vercoutere, Boyan Dimitrov, Marie Laterre, Ephraim Freddy Avni, Isabelle Vandernoot, Julie Désir, Bettina Blaumeiser, Guillaume Smits, Cecile Regnard, Dominique Thomas, Catherine Donner, Kim Van Berkel, Dominique D'Onle, Lionel Van Maldergem, Laureen Rocq, Jean Makhoul, Catheline Vilain, Martina Marangoni, Jamil Soto, Caroline De Coninck, Giulia Garofalo, Anne Massez, Marie-Lucie Racu, Kathelijn Keymolen, Gilles Ceysens, Robert Coulon, Christian Dugauquier, Caroline Daelemans, Anne Holoye, Marie Cassart, Guillaume Debray, Stephanie Romée, Michel Van Rysselberge, Meriem Guizani, Laura Tecco, Valérie Segers, Thomy De Ravel, Elise Brischoux-Boucher, Sara Derisbourg, Isabelle Migeotte, Catherine Houba, Elena Costa, Siham Zaytouni, Sandra Janssens, Kalina Gajewska, Camille Verocq, Christian Norgaard, Nicky D'Haene, Marc Abramowicz, Saskia Bulk, Aurore Stagel-Trabbia, Sarah Bouri, Obstetrics, Clinical sciences, Medical Genetics, and Mother and Child
Subjects: Pediatrics, medicine.medical_specialty, Genetic syndromes, Chromosomal Proteins, Non-Histone, Ultrasonography, Prenatal, Pathology and Forensic Medicine, Fetus, Pregnancy, Prenatal Diagnosis, Genotype, Obstetrics and Gynaecology, Exome Sequencing, Medicine, Humans, Ultrasound abnormalities, Genetics(clinical), Exome, Genetics (clinical), Exome sequencing, Retrospective Studies, business.industry, Genetic variants, Obstetrics and Gynecology, General Medicine, Fetal clinical exome sequencing, Phosphoproteins, Female, Human medicine, business
Abstract: Purpose: We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy. Methods: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy. Results: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes. Conclusion: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
Published: 2022

25. Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group

Author: Léa Guerrini-Rousseau, Julien Masliah-Planchon, Sebastian M Waszak, Pia Alhopuro, Patrick R Benusiglio, Franck Bourdeaut, Ines B Brecht, Giada Del Baldo, Sandeep Kumar Dhanda, Maria Luisa Garrè, Corrie E M Gidding, Steffen Hirsch, Pauline Hoarau, Mette Jorgensen, Christian Kratz, Lucie Lafay-Cousin, Angela Mastronuzzi, Lorenza Pastorino, Stefan M Pfister, Christopher Schroeder, Miriam Jane Smith, Pia Vahteristo, Roseline Vibert, Catheline Vilain, Nicolas Waespe, Ingrid M Winship, D Gareth Evans, Laurence Brugieres, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, ATG - Applied Tumor Genomics, and Biosciences
Subjects: genetic predisposition to disease, GORLIN SYNDROME, genetic counseling, MUTATIONS, congenital, 1184 Genetics, developmental biology, physiology, 610 Medicine & health, CHILDREN, HUMAN HOMOLOG, GENE, PREDISPOSITION, FAMILY, CHILDHOOD MEDULLOBLASTOMA, 360 Social problems & social services, Genetics, central nervous system diseases, and neonatal diseases and abnormalities, 3111 Biomedicine, congenital, hereditary, and neonatal diseases and abnormalities, germ-line mutation, hereditary, Genetics (clinical)
Abstract: BackgroundLittle is known about risks associated with germlineSUFUpathogenic variants (PVs) known as a cancer predisposition syndrome.MethodsTo study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germlineSUFUPV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives withSUFUPV (89 patients) using the Nelson-Aalen estimator.ResultsOverall, 117/172 (68%)SUFUPV carriers developed at least one tumour: medulloblastoma (MB) (86 patients), basal cell carcinoma (BCC) (25 patients), meningioma (20 patients) and gonadal tumours (11 patients). Thirty-three of them (28%) had multiple tumours. Median age at diagnosis of MB, gonadal tumour, first BCC and first meningioma were 1.5, 14, 40 and 44 years, respectively. Follow-up data were available for 160 patients (137 remained alive and 23 died). The cumulative incidence of tumours in relatives was 14.4% (95% CI 6.8 to 21.4), 18.2% (95% CI 9.7 to 25.9) and 44.1% (95% CI 29.7 to 55.5) at the age of 5, 20 and 50 years, respectively. The cumulative risk of an MB, gonadal tumour, BCC and meningioma at age 50 years was: 13.3% (95% CI 6 to 20.1), 4.6% (95% CI 0 to 9.7), 28.5% (95% CI 13.4 to 40.9) and 5.2% (95% CI 0 to 12), respectively. Sixty-four different PVs were reported across the entireSUFUgene and inherited in 73% of cases in which inheritance could be evaluated.ConclusionGermlineSUFUPV carriers have a life-long increased risk of tumours with a spectrum dominated by MB before the age of 5, gonadal tumours during adolescence and BCC and meningioma in adulthood, justifying fine-tuned surveillance programmes.
Published: 2022
Full Text: View/download PDF

26. The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?

Author: Cécile Brachet, Sophie Lhoir, Catheline Vilain, Claudine Heinrichs, Sylvie Tenoutasse, Irina Balikova, Fiorenza Ulgiati, and Emese Boros
Subjects: Adult, Male, medicine.medical_specialty, retina, genetic structures, Adolescent, Endocrinology, Diabetes and Metabolism, Reference range, Triple-A syndrome, Diseases of the endocrine glands. Clinical endocrinology, Redox, chemistry.chemical_compound, Young Adult, Endocrinology, Optical coherence tomography, Ophthalmology, medicine, Humans, In patient, Triple A syndrome, Child, Retrospective Studies, Original Research, Retina, medicine.diagnostic_test, business.industry, Neurodegeneration, neurodegeneration, Retinal, Neurodegenerative Diseases, AAAS, RC648-665, medicine.disease, Prognosis, eye diseases, Esophageal Achalasia, medicine.anatomical_structure, chemistry, ALADIN, OCT, RNFL, Child, Preschool, Optic nerve, Female, sense organs, business, Tomography, Optical Coherence, Adrenal Insufficiency, Follow-Up Studies
Abstract: ObjectiveExperimental evidence suggests that the clinical manifestations of Triple A syndrome result from oxidative stress. Several conditions caused by oxidative stress display retinal involvement. Our objective was to assess the retina and optic nerve involvement in children with Triple A syndrome.MethodsEleven patients with genetically proven Triple A syndrome followed-up in our centre were approached for study participation. The main outcome was the measurement of the thicknesses of the different retinal layers by Optical Coherence Tomography (OCT).Results9 patients with triple A syndrome had OCT measurements. 7 patients were children and 2 were adults; 4 were females and 5 were males. The 7 paediatric patients had at least two OCT measured at a mean interval of 7.9 months after the first one. The average Retinal Nerve Fibre Layer thickness was 74 ± 10 µm in patients compared to the paediatric reference range of 100 ± 2 µm (pConclusions and RelevanceThis is the first study to document retinal layer thicknesses in a series of patients with Triple A syndrome. Nearly all retinal thickness and peripapillary RNFL measurements were very significantly inferior to the reference range in Triple A patients, whatever their age. RNFL thinning was more marked at the temporal part of the optic nerve. OCT being non-invasive, it represents a promising tool to assess the severity of neurodegeneration in patients with Triple A syndrome.
Published: 2021
Full Text: View/download PDF

27. Phenotypes and genotypes in non‐consanguineous and consanguineous primary microcephaly: High incidence of epilepsy

Author: Bettina Blaumeiser, Alec Aeby, Marc Abramowicz, Isabelle Pirson, Cindy Badoer, Helene Verhelst, Kathelijn Keymolen, Berten Ceulemans, Hilde Van Esch, Stéphanie Moortgat, Anne Destree, Patrick Van Bogaert, Sarah Duerinckx, Yusuf Tunca, Valérie Jacquemin, Olivier Vanakker, Nicolas Deconinck, Sarah Weckhuysen, Camille Perazzolo, Marije E.C. Meuwissen, Anna Jansen, Sandrine Passemard, Damien Lederer, Winnie Courtens, Rudy Van Coster, Koenraad Devriendt, Tayeb Sekhara, Nathalie Van der Aa, Isabelle Maystadt, Bart Loeys, Julie Soblet, François-Guillaume Debray, Marie-Cécile Nassogne, Geert Mortier, Julie Désir, Alain Verloes, Catheline Vilain, Jenny Van Den Ende, UCL - (SLuc) Service de neurologie pédiatrique, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de référence en lésions congénitales de la moëlle épinière, UCL - (SLuc) Centre de référence pour l'épilepsie réfractaire, Public Health Sciences, Mental Health and Wellbeing research group, Neurogenetics, Neuroprotection & Neuromodulation, Pediatrics, Clinical sciences, and Medical Genetics
Subjects: Male, Pediatrics, Candidate gene, Microcephaly, ASPM MUTATIONS, PROTEIN, Cell Cycle Proteins, QH426-470, FAMILIES, Consanguinity, Epilepsy, Gene Frequency, Medicine and Health Sciences, SEQUENCE VARIANTS, HETEROGENEITY, Child, Genetics (clinical), SNPS, Genetics & Heredity, Mendeliome, Seizure types, Incidence, primary microcephaly, Phenotype, Cohort, Original Article, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Genotype, rare disease, Nerve Tissue Proteins, ASPM, Genetic Heterogeneity, consanguinity, Genetics, medicine, Humans, PRENATAL-DIAGNOSIS, Molecular Biology, WDR62, Science & Technology, Genetic heterogeneity, business.industry, brain developmental disorders, Généralités, Original Articles, FRAMEWORK, medicine.disease, epilepsy, Human medicine, business
Abstract: Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

28. The ARID1B spectrum in 143 patients

Author: Catherine Vincent-Delorme, Claudia A. L. Ruivenkamp, Marjan De Rademaeker, Francisco Martínez, Tracy Dudding-Byth, Marianne McGuire, Bert B.A. de Vries, Mitsuhiro Kato, Levinus A. Bok, Hülya Kayserili, Jeff M. Milunsky, Suzanne C E H Sallevelt, Alwin F. J. Brouwer, Jill Clayton-Smith, Emilia K. Bijlsma, Miranda Splitt, Patricia G. Wheeler, Philippe M. Campeau, Fatma Mujgan Sonmez, Kylin Lammers, Stefanie Beck-Wödl, Caroline Rooryck, Louise C. Wilson, Evan E. Eichler, Sarina G. Kant, Johanna C. Herkert, Karin R. Heitink, Eyyup Uctepe, Pleuntje J. van der Sluijs, Miho Adachi-Fukuda, Lone W. Laulund, Sandra Jansen, Nicolette S. den Hollander, Damien Lederer, Tomoki Kosho, Constance T. R. M. Stumpel, Saskia M. Maas, Esra Kılıç, Erica H. Gerkes, Duco Steenbeek, Melissa Lees, Kay Metcalfe, Karin Dahan, Ineke van der Burgt, Isabelle Maystadt, Christian Netzer, Ute Grasshoff, Carmen Orellana, Mahmut Şamil Sağıroğlu, Gijs W. E. Santen, Pelin Ozlem Simsek-Kiper, Mónica Roselló, Gabriela Soares, Alexander P.A. Stegmann, Stephen P. Robertson, Adila Al-Kindy, Maian Roifman, Saori Tanabe, Vera Riehmer, Brain H Y Chung, Arie van Haeringen, G. Eda Utine, Yasemin Alanay, Rogier Kersseboom, John B. Moeschler, Barbara Oehl-Jaschkowitz, Katherine Berry, Denise Horn, Alice Gardham, Shane McKee, Anwar Baban, Amparo Sanchis Calvo, Golder N. Wilson, Krystyna H. Chrzanowska, G. M. S. Mancini, Ellen R. Elias, Małgorzata Krajewska-Walasek, Rolph Pfundt, Sarju G. Mehta, Fabienne G. Ropers, Seiji Mizuno, David Hunt, Caroline Pottinger, Dagmar Wieczorek, Yoyo W. Y. Chu, Laurent Pasquier, Bernd Wollnik, Nobuhiko Okamoto, Sunita Venkateswaran, Vanesa López-González, Natalie Canham, Blanca Gener, Anne Destree, Christina Fagerberg, Rachel K. Earl, Sharon N M Olminkhof, Nursel Elcioglu, Charlotte W. Ockeloen, Carlo Marcelis, Samantha A. Vergano, Hermine E. Veenstra-Knol, Anneke T. Vulto-van Silfhout, Allan Bayat, Catheline Vilain, Lucia Solaeche, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA Pat Cytologie (9), Klinische Genetica, van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Woedl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hulya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, Lopez-Gonzalez, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Sanchis Calvo, Amparo, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, Santen, Gijs W. E., Erasmus MC other, Clinical Genetics, Human Genetics, and Acibadem University Dspace
Subjects: Male, 0301 basic medicine, Hypertrichosis, Pediatrics, cuello, bias, Coffin–Siris syndrome, Chromosomal Proteins, Non-Histone, humanos, adolescente, Penetrance, PHENOTYPE, 0302 clinical medicine, Genotype, Intellectual disability, Exome, Coffin-Siris syndrome, Child, mediana edad, Genetics (clinical), Exome sequencing, factores de transcripción, adulto, Middle Aged, estudios de asociación genética, 3. Good health, DNA-Binding Proteins, intellectual disability, Child, Preschool, discapacidad intelectual, penetrancia, Female, Hand Deformities, Congenital, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Adolescent, Micrognathism, Article, CHROMATIN-REMODELING COMPLEX, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, cara, micrognatismo, Human Phenotype Ontology, medicine, Humans, Abnormalities, Multiple, mutación, Long eyelashes, Genetic Association Studies, lactante, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, MUTATIONS, proteínas de unión al ADN, Infant, Newborn, Genetic Variation, Infant, ARID1B, Hand Deformities, Phalanx, medicine.disease, variación genética, deformidades de la mano, exoma, 030104 developmental biology, Face, Mutation, business, Neck, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1BCSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive webbased survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1BID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., We are grateful for the assistance of Pepijn Cox in setting up the website www.arid1bgene.com. This study has made use of data generated by the Human Disease Genes website series, www.humandiseasegenes.com. This work was financially supported by grants from the Netherlands Organisation for Health Research and Development (917-86-319 to B.B.A.d.V., 912-12-109 to B.B.A.d.V.)
Published: 2019

29. Truncating RAX Mutations: Anophthalmia, Hypopituitarism, Diabetes Insipidus, and Cleft Palate in Mice and Men

Author: Catheline Vilain, Cécile Brachet, Claudine Heinrichs, Emese Boros, Julie Soblet, Guillaume Smits, Elena A. Kozhemyakina, Peter H Mathers, and Irina Balikova
Subjects: Male, 0301 basic medicine, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Hypopituitarism, Compound heterozygosity, Biochemistry, Microphthalmia, 0302 clinical medicine, Endocrinology, Missense mutation, Deamino Arginine Vasopressin, Frameshift Mutation, Melatonin, Mice, Knockout, Human Growth Hormone, Antidiuretic Agents, Sciences bio-médicales et agricoles, Magnetic Resonance Imaging, Cleft Palate, Pituitary Gland, endocrine system, medicine.medical_specialty, Hormone Replacement Therapy, Cleft Lip, Context (language use), Frameshift mutation, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Eye Proteins, Clinical Research Articles, Homeodomain Proteins, Anophthalmia, business.industry, Biochemistry (medical), Infant, Newborn, Anophthalmos, medicine.disease, eye diseases, Thyroxine, 030104 developmental biology, Diabetes insipidus, business, Diabetes Insipidus, 030217 neurology & neurosurgery, Transcription Factors
Abstract: The transcription factor RAX is a paired-type homeoprotein that plays a critical role in eye and forebrain development of vertebrate species. RAX knockout mice have anophthalmia, cleft palate, abnormal hypothalamus, and display perinatal lethality. In humans, homozygous or compound heterozygous RAX mutations are reported to cause bilateral micro/anophthalmia without consistent associated features.Congenital Hypopituitarism can be associated with various eye or craniofacial anomalies but the co-occurrence of Congenital Hypopituitarism, anophthalmia, cleft palate and diabetes insipidus is very rare., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

30. Variable expressivity in Buschke-Ollendorff syndrome

Author: A Labadens, Catheline Vilain, Déborah Salik, G. Dupire, Chantal Dangoisse, Guillaume Smits, Ursula Sass, M Marangoni, and D Franck
Subjects: medicine.medical_specialty, business.industry, Genodermatosis, Skin Diseases, Genetic, Dermatology, medicine.disease, Buschke–Ollendorff syndrome, medicine, Humans, Osteopoikilosis, business, Connective tissue nevus
Published: 2021

31. CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

Author: Magalie Barth, Marie-Ange Nguyen-Morel, Marie Le Roux, Florence Renaldo, Nathalie Villeneuve, Florence Riant, Alec Aeby, Lionel Arnaud, Arnaud Biraben, Claude Cances, Catheline Vilain, Anne-Isabelle Vermersch, Patrick Van Bogaert, Edouard Hirsch, Chloé Angelini, Laurence Chaton, Gaetan Lesca, Julien Van Gils, Laurent Villard, Sophie Gueden, Patrick Desbordes de Cepoy, Vincent des Portes, Luc Valton, Cecilia Altuzarra, Audrey Riquet, Anne de Saint Martin, Gall, Valérie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Hôpital Erasme [Bruxelles], CHU Strasbourg, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de Bordeaux Pellegrin [Bordeaux], CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, medicine.medical_specialty, Early onset absence seizures, Stroke-like, [SDV]Life Sciences [q-bio], Status epilepticus, Lamotrigine, CACNA1A, Absence seizure, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Seizures, 030225 pediatrics, medicine, Humans, Spinocerebellar Ataxias, Familial hemiplegic migraine, Drug-resistance, Episodic ataxia, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Lennox-gastaut syndrome, General Medicine, medicine.disease, 3. Good health, Child, Preschool, Pediatrics, Perinatology and Child Health, Ataxia, Female, Neurology (clinical), Calcium Channels, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Lennox–Gastaut syndrome, medicine.drug
Abstract: International audience; CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.
Published: 2021

32. Phenotypes and genotypes in outbred and inbred Primary microcephaly: high incidence of epilepsy

Author: Julie Désir, Catheline Vilain, Sarah Duerinckx, Isabelle Pirson, Olivier Vanakker, Tayeb Sekhara, Bart Loeys, Camille Perazzolo, Marije E.C. Meuwissen, Geert Mortier, Cindy Badoer, Kathelijn Keymolen, Bettina Blaumeiser, Gert Matthijs, Stéphanie Moortgat, Patrick Van Bogaert, Jenneke van den Ende, Yusuf Tunca, Hilde Van Esch, Marc Abramowicz, Julie Soblet, Koen Devriendt, Valérie Jacquemin, Anna Jansen, Sarah Weckhuysen, François-Guillaume Debray, Sandrine Passemard, Damien Lederer, Alain Verloes, Nathalie Van der Aa, Marie-Cécile Nassogne, Helene Verhelst, Alec Aeby, Anne Destree, Winnie Courtens, Isabelle Maystadt, Nicolas Deconinck, Berten Ceulemans, and Rudy Van Coster
Subjects: Oncology, Microcephaly, medicine.medical_specialty, Candidate gene, Genetic heterogeneity, business.industry, Seizure types, medicine.disease, ASPM, Epilepsy, Internal medicine, Cohort, Genotype, medicine, business
Abstract: Primary microcephaly (PM) is defined as a significant reduction in occipito-frontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. We performed detailed phenotypic and genomic analyses in a large cohort (n=169) of patients referred for PM, and could establish a molecular diagnosis in 38 patients. Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in outbred patients (9%). Our series includes 15 previously unreported families and 11 novel pathogenic variants, and we identify novel candidate genes including IGF2BP3, DNAH2, and TSR1. We confirm progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients, with various degrees of severity and seizure types. Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses and improve management of PM patients.
Published: 2021

33. Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype

Author: Ovidiu Balasel, Pauline Dontaine, Véronique Catros, Martine Dassonville, Julie Soblet, Elisa Kottos, Catheline Vilain, Pascale Perlot, Jonchère, Laurent, Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Hearing loss, Spermidine, [SDV]Life Sciences [q-bio], Spermine Synthase, Mutation, Missense, [SDV.GEN] Life Sciences [q-bio]/Genetics, New variant, Enteral administration, 03 medical and health sciences, Epilepsy, Cholestasis, Genetics, medicine, Humans, Exocrine pancreatic insufficiency, Main text, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mendeliome, business.industry, 030305 genetics & heredity, Infant, General Medicine, Failure to thrive, Snyder-Robinson, medicine.disease, 3. Good health, Osteopenia, [SDV] Life Sciences [q-bio], Jejunum, Phenotype, SMS, Child, Preschool, Jejunal Stenosis, Mental Retardation, X-Linked, Spermine, medicine.symptom, business
Abstract: International audience; Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.
Published: 2021

34. New variant in deficiency of interleukin‐36 receptor antagonist syndrome (DITRA)

Author: Samer Zoghaib, Catheline Vilain, Julie Soblet, Déborah Salik, Athanassios Kolivras, Chantal Dangoisse, and Ursula Sass
Subjects: Dermatologie, Interleukin 1 Receptor Antagonist Protein, Text mining, business.industry, Interleukin 36 receptor antagonist, Interleukins, Cancer research, Humans, Psoriasis, Medicine, Dermatology, New variant, business
Abstract: info:eu-repo/semantics/published
Published: 2021

35. BCL11Aframeshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems

Author: Ivan Dimov, Guillaume Smits, Julie Cano-Chervel, Karine Pelc, Catheline Vilain, Simon Baijot, M Sottiaux, Clemens Graf von Kalckreuth, Julie Soblet, and Nicolas Deconinck
Subjects: Male, 0301 basic medicine, Apraxias, Language delay, childhood apraxia of speech, Clinical Reports, Frameshift mutation, 03 medical and health sciences, Exon, Intellectual Disability, BCL11A, Exome Sequencing, Intellectual disability, Genetics, medicine, Humans, Abnormalities, Multiple, Frameshift Mutation, Genetic Association Studies, language delay, Genetics (clinical), Exome sequencing, Comparative Genomic Hybridization, Clinical Report, business.industry, Brain, Facies, Infant, Nuclear Proteins, Sequence Analysis, DNA, Sciences bio-médicales et agricoles, medicine.disease, Hypotonia, Repressor Proteins, Language development, Phenotype, 030104 developmental biology, intellectual disability, Genetic Loci, Childhood apraxia of speech, Muscle Hypotonia, medicine.symptom, Carrier Proteins, business, exome sequencing
Abstract: We report the case of a 7-year-old male of Western European origin presenting with moderate intellectual disability, severe childhood apraxia of speech in the presence of oral and manual dyspraxia, and hypotonia across motor systems including the oral and speech motor systems. Exome sequencing revealed a de novo frameshift protein truncating mutation in the fourth exon of BCL11A, a gene recently demonstrated as being involved in cognition and language development. Making parallels with a previously described patient with a 200 kb 2p15p16.1 deletion encompassing the entire BCL11A gene and displaying a similar phenotype, we characterize in depth how BCL11A is involved in clinical aspects of language development and oral praxis., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017

36. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

Author: Darina Prchalova, Philippe Pm Campeau, Bénédicte Duban-Bedu, Jacques L. Michaud, Marije Koopmans, Arnold Munnich, Christel Depienne, Marilyn Tallot, Fadi F. Hamdan, Eveline Hagebeuk, Marie-Laure Moutard, Anna Kaminska, Petra Laššuthová, Kathryn G. Miller, Ange Line Bruel, Xilma Xr Ortiz-Gonzalez, Shoji Ichikawa, Ingo Helbig, Ethan Em Goldberg, Sarah Weckhuysen, Daphné Lehalle, Elena Gardella, Marie-Bertille Dehouck, Claude Besmond, Patrick Edery, Christine Ioos, Pauline Marzin, Christine Coubes, Julien Buratti, Rima Nabbout, Hubert Journel, Audrey Putoux, Giulia Barcia, Laurence Hubert, Claire Davidson, Berten Ceulemans, Ana Ag Cristancho, Fiona Cunningham, Chloé Quélin, Christèle Dubourg, Aoife Ac McMahon, Thomas Smol, Delphine Héron, Katalin Štěrbová, Katherine Kl Helbig, Boris Keren, Ivan Shelihan, Damien Lederer, Rikke Rs Møller, Emílie Vyhnálková, Alyssa R. Rosen, Natasha Shur, Julie Gauthier, Dragan Marjanovic, Berge Ba Minassian, Marleen Simon, Ledia Brunga, Guillaume Smits, Sandra Janssens, Catheline Vilain, Gaetan Lesca, Caroline Nava, Jasper J. van der Smagt, Laurent Villard, Cyril Mignot, Samuel P. Yang, Joelle Roume, Julie Soblet, JM Pinard, Stéphanie Gobin-Limballe, Bobby P. C. Koeleman, Miroslava Hancarova, Elizabeth J. Donner, Nienke Ne Verbeek, Marie-Line Jacquemont, Marjan J. A. van Kempen, Julia Metreau, David Geneviève, Joannella Morales, Peter M. van Hasselt, Christine Barnerias, Caroline Lacoste, Claire Bar, Thierry Bienvenu, Mathieu Milh, Elsa Rossignol, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), CHU Sainte Justine [Montréal], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de neurologie pédiatrique [CHU Necker], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Cochin [AP-HP], Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, The Hospital for sick children [Toronto] (SickKids), University of Antwerp (UA), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Children’s Hospital of Philadelphia (CHOP ), Hôpital Saint-Vincent de Paul, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Southern Denmark (SDU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University Hospital Motol [Prague], Hôpital Raymond Poincaré [AP-HP], Center for Medical Genetics [Ghent], Ghent University Hospital, University Medical Center [Utrecht], Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CHI Créteil, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Trousseau [APHP], Université de Lyon, CHI Poissy-Saint-Germain, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Antwerp University Hospital [Edegem] (UZA), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Rennes], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en neurosciences de Lyon (CRNL), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: 0301 basic medicine, Male, Génétique clinique, [SDV]Life Sciences [q-bio], Medizin, Physiology, 030105 genetics & heredity, Seizures/epidemiology, Epilepsy, Brain Diseases/epidemiology, X-linked inheritance, Intellectual disability, Guanine Nucleotide Exchange Factors, Protein Isoforms, Missense mutation, Genetics(clinical), 10. No inequality, Non-U.S. Gov't, Genetics (clinical), X-linked recessive inheritance, ComputingMilieux_MISCELLANEOUS, Brain Diseases, Sex Characteristics, Research Support, Non-U.S. Gov't, Brain, Sciences bio-médicales et agricoles, 3. Good health, Pedigree, Phenotype, intellectual disability, Female, Brain/growth & development, Sex characteristics, Génétique moléculaire, Guanine Nucleotide Exchange Factors/genetics, Encephalopathy, Research Support, X-inactivation, Article, 03 medical and health sciences, Seizures, Protein Isoforms/genetics, medicine, Journal Article, IQSEC2, Humans, Intellectual Disability/epidemiology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Infant, Newborn, isoforms, Correction, Infant, medicine.disease, Newborn, Human genetics, 030104 developmental biology, Mutation, epilepsy, Human medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

37. Correction: IQSEC2-related encephalopathy in males and females:a comparative study including 37 novel patients

Author: Petra Laššuthová, Kathryn G. Miller, Jacques L. Michaud, Sarah Weckhuysen, Claude Besmond, Stéphanie Gobin-Limballe, Emílie Vyhnálková, Aoife McMahon, Peter M. van Hasselt, Christine Barnerias, Laurence Hubert, Joannella Morales, Daphné Lehalle, Caroline Lacoste, Rima Nabbout, Hubert Journel, Jasper J. van der Smagt, Patrick Edery, Marjan J. A. van Kempen, Samuel P. Yang, Fiona Cunningham, Thomas Smol, Delphine Héron, Darina Prchalova, David Geneviève, Thierry Bienvenu, Mathieu Milh, Bénédicte Duban-Bedu, Ledia Brunga, Marleen Simon, Ana G. Cristancho, Ethan M. Goldberg, Sandra Janssens, Christel Depienne, Miroslava Hancarova, Shoji Ichikawa, Berge A. Minassian, Ivan Shelihan, Elsa Rossignol, Ange Line Bruel, Elena Gardella, Marije Koopmans, Arnold Munnich, Natasha Shur, Pauline Marzin, Ingo Helbig, Julien Buratti, Alyssa R. Rosen, Giulia Barcia, Claire Davidson, Berten Ceulemans, Marilyn Tallot, Marie Line Jacquemont, Guillaume Smits, Catheline Vilain, Katherine L. Helbig, Gaetan Lesca, Rikke S. Møller, Claire Bar, Marie Laure Moutard, Caroline Nava, Marie Bertille Dehouck, Julie Soblet, Philippe M. Campeau, Cyril Mignot, Laurent Villard, Joelle Roume, Julia Metreau, Dragan Marjanovic, Damien Lederer, Audrey Putoux, Chloé Quélin, Fadi F. Hamdan, Boris Keren, Anna Kaminska, Xilma R. Ortiz-Gonzalez, Christine Ioos, Christine Coubes, Julie Gauthier, Nienke E. Verbeek, Bobby P. C. Koeleman, Eveline Hagebeuk, Jean Marc Pinard, Katalin Štěrbová, Christèle Dubourg, and Elizabeth J. Donner
Subjects: Pediatrics, medicine.medical_specialty, Text mining, business.industry, Published Erratum, Encephalopathy, Medizin, MEDLINE, Medicine, business, medicine.disease, Genetics (clinical)
Abstract: This Article was originally published under Nature Research’s License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
Published: 2019

38. RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy

Author: Patrick Van Bogaert, Jaak Jaeken, Catheline Vilain, Alec Aeby, Geneviève Malfilatre, Damien Lederer, and Cynthia Prigogine
Subjects: Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Pediatrics, medicine.medical_specialty, Glycosylation, 030105 genetics & heredity, Severe epilepsy, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, N-linked glycosylation, medicine, Humans, Early onset, Membrane Glycoproteins, business.industry, Brain, Infant, Video sequence, General Medicine, medicine.disease, Neurology, Mutation, Female, Neurology (clinical), business, Congenital disorder of glycosylation, 030217 neurology & neurosurgery
Abstract: RFT1-congenital disorder of glycosylation (CDG) syndrome, a recessive N-glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non-specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online].
Published: 2016

39. LATE BREAKING NEWS ORAL PRESENTATION

Author: Katrin Õunap, Glenn A. Walter, Sanna Puusepp, Alison M. Barnard, Erica Macke, Peter B. Kang, Carsten G. Bönnemann, Reza Maroofian, Hessa S. Alsaif, Henry Houlden, Sandra Coppens, Andreas Hahn, Volker Straub, Ana Töpf, Nicolas Deconinck, Fowzan S. Alkuraya, Marie Rivera-Zengotita, Catheline Vilain, Sandra Donkervoort, and Anna Lusakowska
Subjects: medicine.medical_specialty, Presentation, History, Neurology, General surgery, media_common.quotation_subject, Pediatrics, Perinatology and Child Health, medicine, Neurology (clinical), Genetics (clinical), media_common
Published: 2020

40. Correction: The ARID1B spectrum in 143 patients

Author: Mitsuhiro Kato, Grazia M.S. Mancini, Krystyna H. Chrzanowska, Alexander P.A. Stegmann, Stephen P. Robertson, Suzanne C E H Sallevelt, Yasemin Alanay, Melissa Lees, Sarju G. Mehta, Anne Destree, Emilia K. Bijlsma, Seiji Mizuno, David Hunt, Laurent Pasquier, H. lya Kayserili, Karin R. Heitink, Ineke van der Burgt, Christian Netzer, Duco Steenbeek, Mónica Roselló, Rachel K. Earl, Sharon N. M. Olminkhof, Arie van Haeringen, Katherine Berry, Ute Grasshoff, Francisco Martínez, Alwin F. J. Brouwer, Nursel Elcioglu, Patricia G. Wheeler, Rolph Pfundt, Shane McKee, Maian Roifman, Yoyo W. Y. Chu, Brain H. Y. Chung, John B. Moeschler, Barbara Oehl-Jaschkowitz, Denise Horn, Karin Dahan, Ellen R. Elias, Natalie Canham, Pelin Ozlem Simsek-Kiper, Vanesa López-González, Samantha A. Vergano, Tracy Dudding-Byth, Esra Kılıç, Charlotte W. Ockeloen, Carlo Marcelis, Levinus A. Bok, Gijs W. E. Santen, Philippe M. Campeau, Kylin Lammers, Anneke T. Vulto-van Silfhout, Stefanie Beck-Wödl, Allan Bayat, Eyyup Uctepe, Louise C. Wilson, Sarina G. Kant, Pleuntje J. van der Sluijs, Fatma Mujgan Sonmez, Tomoki Kosho, Marianne McGuire, Evan E. Eichler, Mahmut Şamil Sağıroğlu, Vera Riehmer, Caroline Rooryck, Miho Adachi-Fukuda, Rogier Kersseboom, Saskia M. Maas, Jeff M. Milunsky, Johanna C. Herkert, Anwar Baban, Nicolette S. den Hollander, Amparo Sanchis Calvo, Lone W. Laulund, Sandra Jansen, Golder N. Wilson, Kay Metcalfe, Fabienne G. Ropers, Caroline Pottinger, Gabriela Soares, Isabelle Maystadt, Miranda Splitt, Constance T. R. M. Stumpel, Catherine Vincent-Delorme, Bert B.A. de Vries, Jill Clayton-Smith, Claudia A. L. Ruivenkamp, Marjan De Rademaeker, Bernd Wollnik, Nobuhiko Okamoto, Christina Fagerberg, Erica H. Gerkes, Damien Lederer, Carmen Orellana, Alice Gardham, Saori Tanabe, Małgorzata Krajewska-Walasek, Adila Al-Kindy, Catheline Vilain, Dagmar Wieczorek, G. Eda Utine, Sunita Venkateswaran, Blanca Gener, Lucia Solaeche, and Hermine E. Veenstra-Knol
Subjects: 0303 health sciences, Coffin–Siris syndrome, Correction, medicine.disease, Genealogy, Spelling, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Intellectual disability, medicine, Psychology, 030217 neurology & neurosurgery, Genetics (clinical), 030304 developmental biology
Abstract: The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.
Published: 2019

41. Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis

Author: Heather C Mefford, Gunnar Buyse, Arvid Suls, Ingo Helbig, Sarah Weckhuysen, Patrick Van Bogaert, Peter De Jonghe, Joseph Cook, Sarah von Spiczak, Ulrich Stephani, Hiltrud Muhle, Corinna Hartmann, and Catheline Vilain
Subjects: Adult, Male, Proband, Adolescent, DNA Copy Number Variations, Fever, Biology, Article, Young Adult, Epilepsy, Dravet syndrome, Gene duplication, medicine, Humans, Copy-number variation, Child, Genetic Association Studies, Chromosome Aberrations, Genetics, Comparative Genomic Hybridization, Middle Aged, medicine.disease, NAV1.1 Voltage-Gated Sodium Channel, Phenotype, Neurology, Child, Preschool, Epilepsy syndromes, Autism, Female, Human medicine, Neurology (clinical), Chromosome Deletion, Comparative genomic hybridization
Abstract: Fever-associated syndromic epilepsies ranging from febrile seizures plus (FS+) to Dravet syndrome have a significant genetic component. However, apart from SCN1A mutations in >80% of patients with Dravet syndrome, the genetic underpinnings of these epilepsies remain largely unknown. Therefore, we performed a genome-wide screening for copy number variations (CNVs) in 36 patients with SCN1A-negative fever-associated syndromic epilepsies. Phenotypes included Dravet syndrome (n = 23; 64%), genetic epilepsy with febrile seizures plus (GEFS+) and febrile seizures plus (FS+) (n = 11; 31%) and unclassified fever-associated epilepsies (n = 2; 6%). Array comparative genomic hybridization (CGH) was performed using Agilent 4 x 180K arrays. We identified 13 rare CNVs in 8 (22%) of 36 individuals. These included known pathogenic CNVs in 4 (11%) of 36 patients: a 1q21.1 duplication in a proband with Dravet syndrome, a 14q23.3 deletion in a proband with FS+, and two deletions at 16p11.2 and 1q44 in two individuals with fever-associated epilepsy with concomitant autism and/or intellectual disability. In addition, a 3q13.11 duplication in a patient with FS+ and two de novo duplications at 7p14.2 and 18q12.2 in a patient with atypical Dravet syndrome were classified as likely pathogenic. Six CNVs were of unknown significance. The identified genomic aberrations overlap with known neurodevelopmental disorders, suggesting that fever-associated epilepsy syndromes may be a recurrent clinical presentation of known microdeletion syndromes.
Published: 2015

42. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Author: Janine Altmüller, Stefan Böhringer, G. Eda Utine, Krystyna H. Chrzanowska, Peter Nürnberg, Maria Teresa Dotti, Marcel Martin, Holger Thiele, Johanna Christina Czeschik, Esra Kılıç, Gunnar Houge, Almuth Caliebe, Sigrid Tinschert, Koray Boduroğlu, Yun Li, Francesca Cristofoli, Filippo Beleggia, Fanny Morice-Picard, Christiane Zweier, Michèle Mathieu Dramard, Joris Vermeesch, Małgorzata Krajewska-Walasek, Beate Albrecht, Hermann-Josef Lüdecke, Ozgur Cogulu, Yasemin Alanay, Annabella Marozza, Hülya Kayserili, Timm O. Goecke, Koenraad Devriendt, Bernd Wollnik, Catheline Vilain, Pelin Ozlem Simsek-Kiper, Esther Pohl, Anita Rauch, Barbara Mikat, Michael Zeschnigk, Nursel Elcioglu, R. Vivarelli, Joussef Hayek, Alma Kuechler, Stanislas Lyonnet, Esther Milz, Dagmar Wieczorek, Sven Rahmann, Encarnación Guillén-Navarro, Blanca Gener, Ludger Klein-Hitpass, Nina Bögershausen, Gilles Morin, Ferda Ozkinay, Alessandra Renieri, Vanesa López-González, Sabine Steiner-Haldenstätt, Andreas Wollstein, Francesca Mari, İç Hastalıkları, Acibadem University Dspace, Wieczorek, Dagmar, Boegershausen, Nina, Beleggia, Filippo, Steiner-Haldenstaett, Sabine, Pohl, Esther, Li, Yun, Milz, Esther, Martin, Marcel, Thiele, Holger, Altmueller, Janine, Alanay, Yasemin, Kayserili, Hulya, Klein-Hitpass, Ludger, Bohringer, Stefan, Wollstein, Andreas, Albrecht, Beate, Boduroglu, Koray, Caliebe, Almuth, Chrzanowska, Krystyna, Cogulu, Ozgur, Cristofoli, Francesca, Czeschik, Johanna Christina, Devriendt, Koenraad, Dotti, Maria Teresa, Elcioglu, Nursel, Gener, Blanca, Goecke, Timm O., Krajewska-Walasek, Malgorzata, Guillen-Navarro, Encarnacion, Hayek, Joussef, Houge, Gunnar, Kilic, Esra, Simsek-Kiper, Pelin Ozlem, Lopez-Gonzalez, Vanesa, Kuechler, Alma, Lyonnet, Stanislas, Mari, Francesca, Marozza, Annabella, Dramard, Michele Mathieu, Mikat, Barbara, Morin, Gilles, Morice-Picard, Fanny, Ozkinay, Ferda, Rauch, Anita, Renieri, Alessandra, Tinschert, Sigrid, Utine, G. Eda, Vilain, Catheline, Vivarelli, Rossella, Zweier, Christiane, Nuernberg, Peter, Rahmann, Sven, Vermeesch, Joris, Luedecke, Hermann-Josef, Zeschnigk, Michael, Wollnik, Bernd, Ege Üniversitesi, and University of Zurich
Subjects: Male, ARID1A, 10039 Institute of Medical Genetics, Chromosomal Proteins, Non-Histone, PHF6, Medizin, Hypotrichosis, Missense mutation, Exome, FORSSMAN-LEHMANN-SYNDROME, INTELLECTUAL DISABILITY, MENTAL-RETARDATION, MUTATIONS, SWI/SNF, COMPLEX, COMPONENTS, ARID1B, SMARCB1, Child, Genetics (clinical), Sequence Deletion, Genetics, Genetics & Heredity, biology, High-Throughput Nucleotide Sequencing, General Medicine, SMARCB1 Protein, Phenotype, Chromatin, DNA-Binding Proteins, Histone, Child, Preschool, Female, Hand Deformities, Congenital, Adult, 2716 Genetics (clinical), Biochemistry & Molecular Biology, Adolescent, Foot Deformities, Congenital, Micrognathism, Mutation, Missense, 610 Medicine & health, Chromatin remodeling, 1311 Genetics, Intellectual Disability, 1312 Molecular Biology, Nucleosome, Humans, Abnormalities, Multiple, Molecular Biology, Infant, Newborn, Facies, Infant, Chromatin Assembly and Disassembly, Repressor Proteins, Face, Karyotyping, biology.protein, 570 Life sciences, Carrier Proteins, Neck, Transcription Factors
Abstract: WOS: 000327800400004, PubMed ID: 23906836, Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. Denovodominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation ( NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies., German Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [01GM1211A, 01GM1211B]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112S398]; ERARE-ANR CraniRareFrench National Research Agency (ANR); German Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [01GS08167]; DFGGerman Research Foundation (DFG) [BO 1955/2-3, WU 314/6-2]; Volkswagen FoundationVolkswagen [86042]; Telethon ItalyFondazione Telethon [GTB12001], This work was part of the CRANIRARE-2 Network funded by the German Federal Ministry of Education and Research (BMBF) (01GM1211A to B. W., 01GM1211B to D. W.), the TUBITAK (112S398 to H. K.) and ERARE-ANR CraniRare to S. L. This work was also funded by a grant (MRNET) from the German Federal Ministry of Education and Research (01GS08167 to D. W.), by DFG grants (BO 1955/2-3 and WU 314/6-2 to S. B. and D. W.) and by the Volkswagen Foundation (ref 86042 to A. W.). The biobank "Cell lines and DNA bank of Rett syndrome, X linked Mental Retardation and other genetic diseases", member of the Telethon Network of Genetic Biobanks (project no. GTB12001), funded by Telethon Italy, provided us with specimens.
Published: 2017

43. First Report on Fetal Cerebral Polyglucosan Bodies in Mucopolysaccharidosis Type VII

Author: Catheline Vilain, Nicky D'Haene, Julie Désir, Valérie Segers, and Hazim Kadhim
Subjects: medicine.medical_specialty, Fetus, Developmental stage, Histologie, Mucopolysaccharidosis, lcsh:RJ1-570, lcsh:Pediatrics, Case Report, General Medicine, Biology, Sciences bio-médicales et agricoles, Psychogénétique, Vacuolated neurons, medicine.disease, 03 medical and health sciences, Female fetus, 0302 clinical medicine, Endocrinology, 030225 pediatrics, Internal medicine, Hydrops fetalis, medicine, Sly disease, Lysosomal storage disease, 030217 neurology & neurosurgery
Abstract: We report on the detection of discordant inclusions in the brain of a 25-week female fetus with a very rare lysosomal storage disease, namely, Sly disease (mucopolysaccharidosis (MPS) type VII), presenting with nonimmune hydrops fetalis. Besides vacuolated neurons, we found abundant deposition of polyglucosan bodies (PGBs) in the developing brain of this fetus in whom MPS-VII was corroborated by lysosomal beta-glucuronidase-deficiency detected in fetal blood and fetal skin-fibroblasts and by the presence of a heterozygous pathogenic variant in the GUSB gene in the mother. Fetal/neonatal metabolic disorders with PGB-deposition are extremely rare (particularly in relation to CNS involvement) and include almost exclusively subtypes of glycogenosis (types IV and VII). The accumulation of PGBs (particularly in the fetal brain) has so far not been depicted in Sly disease. This is the first report on such "aberrant" association. Besides, the detection of these CNS inclusions at such an early developmental stage is remarkably unique., info:eu-repo/semantics/published
Published: 2017

44. A Familial Heterozygous Null Mutation of MET in Autism Spectrum Disorder

Author: Catheline Vilain, Maria-Franca Musumeci, Vanessa Wermenbol, Nelle Lambert, Sandra Acosta, Anne De Leener, Camille Perazzolo, Bruno Pichon, Diana Messina, Barbara Dessars, Marc Abramowicz, and Jelle van den Ameele
Subjects: Genetics, Candidate gene, General Neuroscience, Epigenetics of autism, medicine.disease, Penetrance, Null allele, Frameshift mutation, Autism spectrum disorder, mental disorders, medicine, Autism, Heritability of autism, Neurology (clinical), Psychology, Genetics (clinical)
Abstract: Autism spectrum disorder (ASD) results from interactions of genetic and environmental factors. The MET proto-oncogene has been identified as a candidate gene for autism susceptibility, and is implicated in neurodevelopment and social brain circuitry. Here, we describe the first case of a familial mutation of MET, consisting of an interstitial genomic deletion removing exons 12 through 15, causing a frameshift and premature stop codon, with evidence of nonsense-mediated mRNA decay. On the other allele, patients carried the C allele of the MET promoter rs1858830 polymorphism, known to decrease MET expression and previously associated with autism susceptibility. The heterozygous mutation was associated with autism in one patient, and language and social impairment in a sibling. Our observations delineate the phenotypic spectrum associated with a clearly defined, very likely complete loss of function mutation of MET. Incomplete penetrance in this family was consistent with MET as a partial susceptibility gene for ASD. Implication of MET in normal and pathological brain development opens new perspectives for understanding the pathophysiology of autism and for eventual therapeutical clues.
Published: 2014

45. RASA1Mutations and Associated Phenotypes in 68 Families with Capillary Malformation-Arteriovenous Malformation

Author: Marc Abramowicz, Felicity Collins, Philippe Clapuyt, Christine Léauté-Labrèze, Brid O'Donnell, Julie Désir, Eulalia Baselga, María Antonia González-Enseñat, Antonella Mendola, Nicola Brunetti-Pierri, Yim Dwight, Nicole Revencu, Victoria R. Barrio, David J.E. Lord, Lesley C. Adès, David J. Amor, Mariarosaria Cozzolino, Orli Wargon, Shelagh Joss, Frank Hammer, Susan J. Bayliss, Josée Dubois, Didier Bessis, María del Carmen Boente, Leona Fishman, Wendy K. Chung, Miikka Vikkula, Oon T. Tan, Yolanda Gilaberte, Laurence M. Boon, Cheryl Cytrynbaum, Juliette Mazereeuw-Hautier, Carol A. Gardiner, Patricia E. Burrows, Sarah A. Sandaradura, Fred Ghali, Maria R. Cordisco, Alan D. Irvine, Asunción Vicente, Catheline Vilain, John B. Mulliken, Aicha Salhi, Francine Blei, Loreto Martorell, Anne Dompmartin, Janine Smith, Ashley Wilson, S. Syed, Sarah L. Chamlin, Ana Martín-Santiago, Marie Ange Delrue, Reed E. Pyeritz, Revencu, N, Boon, Lm, Mendola, A, Cordisco, Mr, Dubois, J, Clapuyt, P, Hammer, F, Amor, Dj, Irvine, Ad, Baselga, E, Dompmartin, A, Syed, S, Martin Santiago, A, Ades, L, Collins, F, Smith, J, Sandaradura, S, Barrio, Vr, Burrows, Pe, Blei, F, Cozzolino, M, BRUNETTI PIERRI, Nicola, Vicente, A, Abramowicz, M, D?sir, J, Vilain, C, Chung, Wk, Wilson, A, Gardiner, Ca, Dwight, Y, Lord, Dj, Fishman, L, Cytrynbaum, C, Chamlin, S, Ghali, F, Gilaberte, Y, Joss, S, Boente Mdel, C, L?aut? Labr?ze, C, Delrue, Ma, Bayliss, S, Martorell, L, Gonz?lez Ense?at, Ma, Mazereeuw Hautier, J, O'Donnell, B, Bessis, D, Pyeritz, Re, Salhi, A, Tan, Ot, Wargon, O, Mulliken, Jb, and Vikkula, M.
Subjects: Male, Pathology, medicine.medical_specialty, Capillary malformation, DNA Mutational Analysis, Port-Wine Stain, Sturge–Weber syndrome, arteriovenous malformation, P120 GTPase Activating Protein, Sturge-Weber syndrome, Biology, medicine.disease_cause, Arteriovenous Malformations, Gene Order, Genetics, medicine, Humans, Prospective Studies, Allele, Genetic Association Studies, Genetics (clinical), Retrospective Studies, Mutation, capillary malformation, p120 GTPase Activating Protein, Arteriovenous malformation, medicine.disease, Parkes Weber syndrome, Capillaries, Glomuvenous malformation, Phenotype, Amino Acid Substitution, Female, RASA1
Abstract: Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n=100), common CM(s) (port-wine stain; n=100), Sturge-Weber syndrome (n=37), or isolated AVM(s) (n=24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the second-hit hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up. (C) 2013 Wiley Periodicals, Inc.
Published: 2013

46. Mosaic parental germline mutations causing recurrent forms of malformations of cortical development

Author: François Artiguenave, Jamel Chelly, Bettina Bessières, Imen Rejeb, Catherine Fallet-Bianco, Giuseppe Muraca, Catheline Vilain, Adrienne Elmorjani, Nadia Bahi-Buisson, Nicolas Lebrun, Hélène Maurey, Julia Lauer Zillhardt, Sylvie Odent, Yuri Musizzano, Karine Poirier, Nicole Philip, David Geneviève, Cécile Masson, Stanislas Lyonnet, Yoann Saillour, Robert Olaso, Jelena Martinovic, Jean-François Deleuze, Lucile Pinson, Lamia Ben Jemaa, François Rivier, Juliette Nectoux, Patrick Van Bogaert, Anne Boland, Fabienne Giuliano, Patrick Nitschke, Loic Broix, Nicolas Leboucq, Cherif Beldjord, Nicole Bigi, Olivier Dulac, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biochimie et biologie moléculaire, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie et biologie cellulaire, Université de Montréal (UdeM)-Hôpital Sainte-Justine, CHU Necker - Enfants Malades [AP-HP], Service de Neurologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Reference Epilepsies Rares-CHU Necker - Enfants Malades [AP-HP], Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique clinique [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, CHU Pontchaillou [Rennes], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Centre Hospitalier Régional et Universitaire, Service de génétique médicale, Hôpital l'Archet, Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Génétique Médicale, Université libre de Bruxelles (ULB), Service Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de biochimie et génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP], Hôpital Sainte-Justine-Université de Montréal, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre de Reference Epilepsies Rares-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Université Libre de Bruxelles [Bruxelles] (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Centre de Reference Epilepsies Rares-CHU Necker - Enfants Malades [AP-HP], NeuroSpin, Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut d'imagerie biomédicale (I²BM), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Service de Neuropédiatrie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Plate Forme Paris Descartes de Bioinformatique ( BIP-D ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), and Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Adult, Male, Candidate gene, [SDV]Life Sciences [q-bio], Short Report, Biology, Bioinformatics, Germline, 03 medical and health sciences, Germline mutation, Genetics, Syntaxin, Humans, Exome, Sibling, Genetics (clinical), Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, [ SDV ] Life Sciences [q-bio], Mosaicism, Qa-SNARE Proteins, Malformation of cortical development, 3. Good health, Pedigree, Malformations of Cortical Development, 030104 developmental biology, Genetic Loci, Female
Abstract: International audience; To unravel missing genetic causes underlying monogenic disorders with recurrence in sibling, we explored the hypothesis of parental germline mosaic mutations in familial forms of malformation of cortical development (MCD). Interestingly, four families with parental germline variants, out of 18, were identified by whole-exome sequencing (WES), including a variant in a new candidate gene, syntaxin 7. In view of this high frequency, revision of diagnostic strategies and reoccurrence risk should be considered not only for the recurrent forms, but also for the sporadic cases of MCD
Published: 2016

47. Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Author: Marie, Vincent, David, Geneviève, Agnès, Ostertag, Sandrine, Marlin, Didier, Lacombe, Dominique, Martin-Coignard, Christine, Coubes, Albert, David, Stanislas, Lyonnet, Catheline, Vilain, Anne, Dieux-Coeslier, Sylvie, Manouvrier, Bertrand, Isidor, Marie-Line, Jacquemont, Sophie, Julia, Valérie, Layet, Sophie, Naudion, Sylvie, Odent, Laurent, Pasquier, Sybille, Pelras, Nicole, Philip, Geneviève, Pierquin, Fabienne, Prieur, Nisrine, Aboussair, Tania, Attie-Bitach, Geneviève, Baujat, Patricia, Blanchet, Catherine, Blanchet, Hélène, Dollfus, Bérénice, Doray, Elise, Schaefer, Patrick, Edery, Fabienne, Giuliano, Alice, Goldenberg, Cyril, Goizet, Agnès, Guichet, Christian, Herlin, Laetitia, Lambert, Bruno, Leheup, Jelena, Martinovic, Sandra, Mercier, Cyril, Mignot, Marie-Laure, Moutard, Marie-José, Perez, Lucile, Pinson, Jacques, Puechberty, Marjolaine, Willems, Hanitra, Randrianaivo, Kateline, Szakszon, Kateline, Szaskon, Annick, Toutain, Alain, Verloes, Jacqueline, Vigneron, Elodie, Sanchez, Pierre, Sarda, Jean-Louis, Laplanche, Corinne, Collet, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Génétique Humaine, Université de Liège-CHU Liège, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre [Strasbourg], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Groupe de recherche clinique 'déficience intellectuelle et autisme', Université Pierre et Marie Curie - Paris 6 (UPMC), Unité fonctionnelle de neurogénétique moléculaire et cellulaire, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut National de la Santé et de la Recherche Médicale, Head of the Department of Medical Genetics, Service de Génétique Clinique et Université Lille 2, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Centre de recherche en neurosciences de Lyon ( CRNL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Génétique [Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Bretonneau-CHRU Tours, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Lavoisier de Versailles ( ILV ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Adult, Male, 0301 basic medicine, Franceschetti syndrome, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Biology, Treacher Collins syndrome, Young Adult, 03 medical and health sciences, medicine, Humans, Base sequence, POLR1D, Amino Acid Sequence, Child, Genetic Association Studies, Ribonucleoprotein, U5 Small Nuclear, Genetics (clinical), Sequence Deletion, phenotype–genotype correlations, Base Sequence, [ SDV ] Life Sciences [q-bio], Nuclear Proteins, Large series, DNA-Directed RNA Polymerases, Mandibulofacial dysostosis, Middle Aged, Peptide Elongation Factors, Phosphoproteins, medicine.disease, Dermatology, 3. Good health, Surgery, TCOF1, 030104 developmental biology, Mutation, Microcephaly, Female, Mandibulofacial Dysostosis
Abstract: International audience; Purpose - Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. Methods - We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. Results - We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Conclusion - Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
Published: 2016

48. Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis

Author: Ian Young, Sara MacKay, Klaus Zerres, Jenny Morton, Fabio De Leonardis, Lihadh Al-Gazali, Beyhan Tüysüz, Céline Huber, Geert Mortier, Antonio Rossi, Arnold Munnich, Erkan Koparir, Julie Désir, Mathilde Nizon, Yasemin Alanay, Mélanie Fradin, Martine Le Merrer, Antonella Forlino, Valérie Cormier-Daire, Carine Le Goff, Rodolphe Merrina, Catheline Vilain, Bassam Abu-Libdeh, Jill Clayton-Smith, Sarenur Basaran, Marie T. Greally, Beate Albrecht, Harinder Gill, David Sillence, Merel C van Maarle, Acibadem University Dspace, and Human Genetics
Subjects: Joint Instability, Spondyloepiphyseal dysplasia, Sulfotransferase, CHST3, Dwarfism, Biology, medicine.disease_cause, Craniofacial Abnormalities, Nucleotidases, proteoglycan metabolism, Genetics, medicine, Humans, CANT1, Glycosides, Gene, Cells, Cultured, Research Articles, Genetics (clinical), Mutation, Polydactyly, Ossification, Ossification, Heterotopic, medicine.disease, Phenotype, Chromatography, Gel, Proteoglycans, Human medicine, Sulfotransferases, medicine.symptom, Desbuquois dysplasia type 1 and type 2
Abstract: Desbuquois dysplasia (DD) is characterized by antenatal and postnatal short stature, multiple dislocations, and advanced carpal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. We have identified mutations in calcium activated nucleotidase 1 gene (CANT1) in DD type 1. Recently, CANT1 mutations have been reported in the Kim variant of DD, characterized by short metacarpals and elongated phalanges. DD has overlapping features with spondyloepiphyseal dysplasia with congenital joint dislocations (SDCD) due to Carbohydrate (chondroitin 6) Sulfotransferase 3 (CHST3) mutations. We screened CANT1 and CHST3 in 38 DD cases (6 type 1 patients, 1 Kim variant, and 31 type 2 patients) and found CANT1 mutations in all DD type 1 cases, the Kim variant and in one atypical DD type 2 expanding the clinical spectrum of hand anomalies observed with CANT1 mutations. We also identified in one DD type 2 case CHST3 mutation supporting the phenotype overlap with SDCD. To further define function of CANT1, we studied proteoglycan synthesis in CANT1 mutated patient fibroblasts, and found significant reduced GAG synthesis in presence of beta-D-xyloside, suggesting that CANT1 plays a role in proteoglycan metabolism. Hum Mutat 33:1261-1266, 2012. (c) 2012 Wiley Periodicals, Inc.
Published: 2012

49. Iodotyrosine Deiodinase Defect Identified via Genome-Wide Approach

Author: Isabelle Pirson, Bernard Corvilain, Agnès Burniat, Marc Abramowicz, Willem Kulik, Rodrigo Moreno-Reyes, Gijs B. Afink, Catheline Vilain, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, Other Research, and Center for Reproductive Medicine
Subjects: Male, endocrine system, medicine.medical_specialty, Goiter, endocrine system diseases, Endocrinology, Diabetes and Metabolism, DNA Mutational Analysis, Clinical Biochemistry, Context (language use), Iodide Peroxidase, Biochemistry, Consanguinity, Young Adult, chemistry.chemical_compound, Endocrinology, Hypothyroidism, Internal medicine, medicine, Humans, Point Mutation, music, Diiodotyrosine, music.instrument, Genome, Human, business.industry, Siblings, Homozygote, Biochemistry (medical), Thyroid, Monoiodotyrosine, medicine.disease, Iodine deficiency, Pedigree, Congenital hypothyroidism, medicine.anatomical_structure, chemistry, Child, Preschool, Iodotyrosine deiodinase, Female, business
Abstract: Context: Diagnosis of congenital hypothyroidism is hampered by the heterogeneity of inborn errors of thyroid metabolism and the possible delay in hypothyroidism development leading to missed cases by neonatal screen. Objective: In the current study, we used a whole-genome approach to identify the mutation responsible for severe hypothyroidism and a huge goiter in the eldest child born to healthy first cousins. Results: We identified a homozygous mutation of the iodotyrosine deiodinase gene (IYD). We delineated the phenotype of this defect in detail, including urinary monoiodotyrosine (MIT) and diiodotyrosine (DIT) excretion. Moreover, a 4.5-yr-old sister was found homozygous for the mutation. Her clinical and biological data were normal, except for elevated MIT and DIT excretion. The urinary loss of MIT and DIT iodine observed in most affected individuals was quite limited compared to the total iodine loss, except for the hypothyroid homozygote. Hypothyroidism could therefore be partially induced by a relative iodine deficiency caused by urinary iodine loss through MIT and DIT excretion, even in cases of normal iodine intake. The wide inter-and intrafamilial variability of the disease severity remains unclear. Conclusions: Besides refining the phenotype of the IYD defect, our observation shows that a global, genome-wide approach to the heterogeneous inborn thyroid defects was efficient in rapidly identifying the mutation in the proband and the disease recurrence in the still euthyroid sister. Although facilitated by consanguinity in this family, novel sequencing techniques will soon make whole-genome approaches readily amenable to more common cases. (J Clin Endocrinol Metab 97: E1276-E1283, 2012)
Published: 2012

50. A new mutation of carbonic anhydrase 8 gene expanding the cerebellar ataxia, mental retardation and disequilibrium syndrome (CAMRQ) subtype 3

Author: Julie Soblet, Catheline Vilain, Guillaume Smits, Nicolas Deconinck, Alec Aeby, and Lionel Paternoster
Subjects: Genetics, biology, Cerebellar ataxia, 05 social sciences, 050105 experimental psychology, Disequilibrium syndrome, 03 medical and health sciences, 0302 clinical medicine, Neurology, Carbonic anhydrase, New mutation, biology.protein, medicine, 0501 psychology and cognitive sciences, Neurology (clinical), medicine.symptom, Gene, 030217 neurology & neurosurgery
Published: 2017

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

85 results on '"Catheline, Vilain"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources