13 results on '"Sole G"'
Search Results
2. Fetal phenotypes in otopalatodigital spectrum disorders.
- Author
-
Naudion S, Moutton S, Coupry I, Sole G, Deforges J, Guerineau E, Hubert C, Deves S, Pilliod J, Rooryck C, Abel C, Le Breton F, Collardeau-Frachon S, Cordier MP, Delezoide AL, Goldenberg A, Loget P, Melki J, Odent S, Patrier S, Verloes A, Viot G, Blesson S, Bessières B, Lacombe D, Arveiler B, Goizet C, and Fergelot P
- Subjects
- Craniofacial Abnormalities diagnosis, Craniofacial Abnormalities metabolism, DNA Mutational Analysis, Female, Hand Deformities, Congenital diagnosis, Hand Deformities, Congenital metabolism, Humans, Infant, Newborn, Male, Osteochondrodysplasias diagnosis, Osteochondrodysplasias metabolism, Pedigree, Craniofacial Abnormalities genetics, Fetus, Filamins genetics, Hand Deformities, Congenital genetics, Mutation, Osteochondrodysplasias genetics, Phenotype
- Abstract
Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
3. [Charcot-Marie-Tooth disease associated with periaxin mutations (CMT4F): Clinical, electrophysiological and genetic analysis of 24 patients].
- Author
-
Renouil M, Stojkovic T, Jacquemont ML, Lauret K, Boué P, Fourmaintraux A, Randrianaivo H, Tallot M, Mignard D, Roelens P, Tabailloux D, Bernard R, Cartault F, Chane-Thien E, Dubourg O, Ferrer X, Sole G, Fournier E, Latour P, Lacour A, and Mignard C
- Subjects
- Adult, Charcot-Marie-Tooth Disease diagnosis, Child, Child, Preschool, Cohort Studies, Electrophysiology, Family, Female, France, Humans, Infant, Male, Reunion, Young Adult, Charcot-Marie-Tooth Disease genetics, Charcot-Marie-Tooth Disease physiopathology, Membrane Proteins genetics, Mutation
- Abstract
Autosomal recessive Charcot-Marie-Tooth disease (AR-CMT) is often characterized by onset in early childhood and severe phenotype compared to the dominant forms. CMT disease associated with periaxin gene (PRX) is rare and characterized by demyelination limited to the major peripheral nerves. Following the discovery of a high frequency of a specific periaxin gene mutation (E1085fsX4 homozygote) in the Reunion Island, we examined all French patients known as carriers of the periaxin gene mutation. There were 24 patients. Eighteen were from the Reunion Island (6 families and 10 sporadic cases). The six remaining patients were in two families, each with two affected individuals, and two sporadic cases. The series included 17 female and seven male patients. Walking was acquired late, on average at 3.4±1.6 years. One patient never learned to walk. The Charcot Marie Tooth Neuropathy Score (CMTNS) averaged 24.5±8.1. Seven patients had been wheelchair-bound since the age of 24±22. Other symptoms were: scoliosis most often observed after the age of 12 years and sometimes complicated by a restrictive respiratory syndrome; foot deformity in 24 patients; strabismus; glaucoma; myopia. When conduction recordings are available, median nerve motor conduction was slow (<10m/s), associated with a major lengthening of distal latencies. Study of the periaxin gene should be considered in patients with severe demyelinating neuropathy associated with early infantile scoliosis. This disease leads to major disability (29% of patients in this series were wheelchair-bound) and to respiratory insufficiency. Genetic counselling is highly recommended for consanguineous families., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
4. A French family with Charcot-Marie-Tooth disease related to simultaneous heterozygous MFN2 and GDAP1 mutations.
- Author
-
Vital A, Latour P, Sole G, Ferrer X, Rouanet M, Tison F, Vital C, and Goizet C
- Subjects
- Adult, Aged, Biopsy, Charcot-Marie-Tooth Disease pathology, Child, Preschool, Female, France, Humans, Male, Middle Aged, Peroneal Nerve pathology, Phenotype, Charcot-Marie-Tooth Disease ethnology, Charcot-Marie-Tooth Disease genetics, GTP Phosphohydrolases genetics, Heterozygote, Mitochondrial Proteins genetics, Mutation genetics, Nerve Tissue Proteins genetics
- Abstract
Either dominantly inherited mutations in MFN2 encoding mitofusin 2 or GDAP1 encoding ganglioside-induced differentiation associated protein 1 may be associated with mild neuropathy. The proband, a 41-year-old woman, and her daughter present a severe axonal form of Charcot-Marie-Tooth (CMT) disease. Both are heterozygous for the well-described mild variant p.R120W in GDAP1, which was transmitted by the pauci symptomatic proband's mother. Given that they had an early onset in the first decade and delayed walking acquisition, the other genes implicated in axonal forms of CMT disease were analyzed. A second mutation truncating MFN2 (p.Val160fsX26) was found in the proband and her daughter. This mutation was transmitted by the proband's father who has normal neurological examination. The proband underwent two nerve biopsies which showed an axonal degeneration, myelin modifications, and intra-axonal mitochondria with distorted cristae. Such abnormal mitochondria have been reported in cases with autosomal dominant MFN2 mutations and in one patient with an autosomal recessive GDAP1 mutation. Our two cases show that heterozygous truncation of MFN2, which is silent at least until the sixth decade, when combined with the mild p.R120W GDAP1 variant, leads to a severe neuropathy. This supports the emerging hypothesis of cumulative effects of MFN2 and GDAP1 mutation., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
5. TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review.
- Author
-
Martin-Negrier ML, Sole G, Jardel C, Vital C, Ferrer X, and Vital A
- Subjects
- Biopsy, Blotting, Southern, DNA, Mitochondrial genetics, Female, France, Humans, Male, Middle Aged, Mitochondrial Proteins, Muscle, Skeletal pathology, Ophthalmoplegia, Chronic Progressive External pathology, Ophthalmoplegia, Chronic Progressive External physiopathology, Pedigree, Polymerase Chain Reaction, Young Adult, DNA Helicases genetics, Mutation, Ophthalmoplegia, Chronic Progressive External genetics
- Abstract
Background: Multiple mitochondrial DNA (mtDNA) deletions usually have a mendelian inheritance secondary to mutation in nuclear genes. One of these is the Twinkle gene whose mutation is responsible for autosomal dominant progressive external ophthalmoplegia (PEO). The number of reported cases with mainly myopathic symptoms and possible nervous system involvement related to Twinkle gene mutation is limited. We present a new French family of whom two members displayed myopathy and neuropathy associated with PEO, and we perform a clinical review in light of other observations reported in the literature., Methods: The proband, one son and the daughter have been investigated. Southern blot analysis and long-range PCR assay have been performed from muscle biopsy specimens. Coding exons and flanking intron regions of polymerase gamma (POLG) and DNA helicase (Twinkle) genes were sequenced., Results: Multiple mitochondrial DNA deletions have been found and sequencing of the Twinkle gene showed the change p.R374Q., Conclusion: Two other families from the literature also had the R374Q mutation. Symptoms reported in association with this mutation were myopathy, peripheral neuropathy, dysarthria and/or dysphagia, respiratory insufficiency and parkinsonism. Respiratory insufficiency caused by chest wall weakness was reported in other families with different Twinkle gene mutations, and one might provide exercise intolerance, dysarthria and/or dysphagia as symptoms in favor of the diagnosis. Occurrence of impressive emaciation was a peculiarity in our family., (© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.)
- Published
- 2011
- Full Text
- View/download PDF
6. SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum.
- Author
-
Goizet C, Boukhris A, Maltete D, Guyant-Maréchal L, Truchetto J, Mundwiller E, Hanein S, Jonveaux P, Roelens F, Loureiro J, Godet E, Forlani S, Melki J, Auer-Grumbach M, Fernandez JC, Martin-Hardy P, Sibon I, Sole G, Orignac I, Mhiri C, Coutinho P, Durr A, Brice A, and Stevanin G
- Subjects
- Adolescent, Brain diagnostic imaging, Brain pathology, Child, Corpus Callosum diagnostic imaging, Female, Humans, Magnetic Resonance Imaging, Male, Positron-Emission Tomography methods, Severity of Illness Index, Spastic Paraplegia, Hereditary diagnostic imaging, Tomography, Emission-Computed, Single-Photon methods, Carrier Proteins genetics, Corpus Callosum pathology, Mutation, Spastic Paraplegia, Hereditary genetics, Spastic Paraplegia, Hereditary pathology
- Abstract
Objective: Hereditary spastic paraplegias (HSPs) are very heterogeneous inherited neurodegenerative disorders. Our group recently identified ZFYVE26 as the gene responsible for one of the clinical and genetic entities, SPG15. Our aim was to describe its clinical and mutational spectra., Methods: We analyzed all exons of SPG15/ZFYVE26 gene by direct sequencing in a series of 60 non-SPG11 HSP subjects with associated mental or MRI abnormalities, including 30 isolated cases. The clinical data were collected through the SPATAX network., Results: We identified 13 novel truncating mutations in ZFYVE26, 12 of which segregated at the homozygous or compound heterozygous states in 8 new SPG15 families while 1 was found at the heterozygous state in a single family. Two of 3 splice site mutations were validated on mRNA of 2 patients. The SPG15 phenotype in 11 affected individuals was characterized by early onset HSP, severe progression of the disease, and mental impairment dominated by cognitive decline. Thin corpus callosum and white matter hyperintensities were MRI hallmarks of the disease in this series., Conclusions: The mutations are truncating, private, and distributed along the entire coding sequence of ZFYVE26, which complicates the analysis of this gene in clinical practice. In our series of patients with hereditary spastic paraplegia-thin corpus callosum, the largest analyzed so far, SPG15 was the second most frequent form (11.5%) after SPG11. Both forms share similar clinical and imaging presentations with very few distinctions, which are, however, insufficient to infer the molecular diagnosis when faced with a single patient.
- Published
- 2009
- Full Text
- View/download PDF
7. Myocilin Gln368stop mutation and advanced age as risk factors for late-onset primary open-angle glaucoma.
- Author
-
Angius A, Spinelli P, Ghilotti G, Casu G, Sole G, Loi A, Totaro A, Zelante L, Gasparini P, Orzalesi N, Pirastu M, and Bonomi L
- Subjects
- Age Factors, Age of Onset, Aged, Aged, 80 and over, Cytoskeletal Proteins, DNA analysis, DNA Mutational Analysis, DNA Probes chemistry, Female, Humans, Male, Middle Aged, Ocular Hypertension genetics, Pedigree, Risk Factors, Codon, Terminator genetics, Eye Proteins genetics, Glaucoma, Open-Angle genetics, Glycoproteins genetics, Mutation
- Abstract
Background: Juvenile open-angle glaucoma has been found to be associated with molecular defects in the myocilin (MYOC) gene. Most of the defects are missense mutations located in the third exon. The Gln368stop mutation has recently been found in several cases of late-onset primary open-angle glaucoma (POAG)., Objective: To study the effect of glaucoma risk in a relatively homogeneous genetic population., Methods: A clinical study was performed in all living members of a 5-generation family. DNA analysis was performed for studying association with genetic markers and identifying the mutation., Results: We identified the Gln368stop molecular defect in 19 patients with POAG, 5 patients with ocular hypertension, and 22 healthy carriers. We compared affected and unaffected carriers based on age at onset and last examination, respectively. Besides the presence of 3 young patients with POAG (<40 years old), the number of glaucomatous patients in the advanced age group increased., Conclusions: The penetrance of glaucoma increases with age in Gln368stop carriers, but some remain unaffected at advanced age and others are affected at an early age. This suggests that additional risk factors are operating within this family, which may be identified by a genome-wide linkage search in this large pedigree., Clinical Relevance: The myocilin Gln368stop mutation shows a good genotype-phenotype correlation and should be investigated in all familiar cases of chronic POAG. This may be important for early diagnosis and periodical checkups of presymptomatic individuals belonging to these families.
- Published
- 2000
- Full Text
- View/download PDF
8. A novel mutation in the GLC1A gene causes juvenile open-angle glaucoma in 4 families from the Italian region of Puglia.
- Author
-
Angius A, De Gioia E, Loi A, Fossarello M, Sole G, Orzalesi N, Grignolo F, Cao A, and Pirastu M
- Subjects
- Adolescent, Adult, Child, Cytoskeletal Proteins, DNA Mutational Analysis, DNA Primers, Exons, Female, Genetic Linkage, Glaucoma, Open-Angle pathology, Humans, Italy, Male, Middle Aged, Pedigree, Sequence Analysis, DNA, Visual Field Tests, Eye Proteins genetics, Glaucoma, Open-Angle genetics, Glycoproteins genetics, Mutation
- Abstract
Background: Primary open-angle glaucoma encompasses a complex of potentially blinding ocular diseases characterized by a normal-appearing angle of the anterior chamber, a characteristic degeneration of the optic nerve with resultant typical visual field defects, and usually, an elevated intraocular pressure. It can be subdivided into 2 groups according to the age at onset: the more prevalent chronic open-angle glaucoma diagnosed after 40 years of age, and the less common juvenile form, which occurs between 3 years of age and early adulthood. A locus for primary open-angle glaucoma (GLC1A) has been mapped to a 3-centimorgan region of the long arm of chromosome 1 (1q23-25). Recently, the myocilin (MYOC) gene, located in this chromosomal interval, has been found mutated in several patients affected by primary open-angle glaucoma., Objective: To describe the clinical and molecular genetic features of 4 pedigrees affected by autosomal dominant juvenile open-angle glaucoma, all from the Italian region of Puglia., Methods: Clinical study, gonioscopy, automated perimetry, and DNA analysis were performed on several members of the 4 families., Results: We identified a new molecular defect (1177GACA-->T) in the third exon of the GLC1A gene. This mutation is present in all affected persons and in 2 still phenotypically normal persons., Conclusion: Our results are important for diagnostic purposes because it is now possible to identify asymptomatic carriers, for whom clinical surveillance for the early detection and treatment of glaucoma may be suggested.
- Published
- 1998
- Full Text
- View/download PDF
9. A common beta ig-h3 gene mutation (delta f540) in a large cohort of Sardinian Reis Bücklers corneal dystrophy patients. Mutations in brief no. 180. Online.
- Author
-
Rozzo C, Fossarello M, Galleri G, Sole G, Serru A, Orzalesi N, Serra A, and Pirastu M
- Subjects
- Chromosomes, Human, Pair 5 genetics, Humans, Transforming Growth Factor beta genetics, Corneal Dystrophies, Hereditary genetics, Extracellular Matrix Proteins, Mutation genetics, Neoplasm Proteins genetics
- Abstract
Reis-Bücklers' corneal dystrophy (RBCD) is a relatively rare autosomal dominant disease originating in the Bowman's membrane, which causes severe visual impairment. Recently RBCD, together with lattice corneal dystrophy type I (LCDI), granular corneal dystrophy (CDGG1) and Avellino stromal dystrophy (ASD), all mapped on 5q31, were found to be associated to four different mutations in the beta ig-h3 gene which codify for kerato-epithelin. We identified several cases of RBCD in Sardinia. We reconstructed through genealogical search two eight generation-families, originating from the same village (Arbus), indicating a common ancestor for RBCD in Sardinia. Linkage studies on these families confirmed the association of the disease with the 5q31 region. Sequence analysis of beta ig-h3 gene revealed a trinucleotide deletion in exon 12, corresponding to the loss of F540 in the protein sequence (delta F540). Our data describe a new mutation in the beta ig-h3 gene causing RBCD. This dominant negative mutation is located in the fourth internal repeat of kerato-epithelin which is a protein domain highly conserved across species. This suggests the basic role of this domain in maintaining the proper kerato-epithelin structure which when altered can cause the typical precipitates in the RBCD cornea.
- Published
- 1998
10. Fetal phenotypes in otopalatodigital spectrum disorders
- Author
-
Naudion, S., Moutton, S., Coupry, I., Sole, G., Deforges, J., Guerineau, E., Hubert, Cédric, Deves, S., Pilliod, J., Rooryck, C., Abel, C., Le Breton, F., Collardeau-Frachon, S., Cordier, M. P., Delezoide, A. L., Goldenberg, A., Loget, P., Melki, J., Odent, S., Patrier, S., Verloes, A., Viot, G., Blesson, S., Bessières, B., Lacombe, D., Arveiler, B., Goizet, C., Fergelot, P., CHU Bordeaux [Bordeaux], Neurogénétique moléculaire, Université d'Évry-Val-d'Essonne (UEVE) - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité fonctionnelle de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré - Université Paris Diderot - Paris 7 (UPD7), AP-HP Hôpital Necker - Enfants Malades [Paris], Laboratoire de Génétique Humaine, Développement et Cancer, Université Bordeaux Segalen - Bordeaux 2, Service de génétique médicale, Université de Bordeaux (UB) - CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Université d'Évry-Val-d'Essonne (UEVE)-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 National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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 Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), 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 ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)
- Subjects
Male ,[SDV]Life Sciences [q-bio] ,Filamins ,DNA Mutational Analysis ,Infant, Newborn ,Melnick-Needles ,Otopalatodigital ,frontometaphyseal dysplasia ,Osteochondrodysplasias ,MNS ,OPD2 ,Pedigree ,FMD ,FLNA ,Craniofacial Abnormalities ,[SDV] Life Sciences [q-bio] ,Fetus ,Phenotype ,Mutation ,Humans ,filamin A ,Female ,Hand Deformities, Congenital - Abstract
International audience; Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick–Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra‐skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.
- Published
- 2016
11. A common beta ig-h3 gene mutation (delta f540) in a large cohort of Sardinian Reis Bücklers corneal dystrophy patients. Mutations in brief no. 180. Online
- Author
-
Rozzo, C., Fossarello, M., Grazia Galleri, Sole, G., Serru, A., Orzalesi, N., Serra, A., and Pirastu, M.
- Subjects
Corneal Dystrophies, Hereditary ,Extracellular Matrix Proteins ,Transforming Growth Factor beta ,Mutation ,Chromosomes, Human, Pair 5 ,Humans ,Neoplasm Proteins - Abstract
Reis-Bücklers' corneal dystrophy (RBCD) is a relatively rare autosomal dominant disease originating in the Bowman's membrane, which causes severe visual impairment. Recently RBCD, together with lattice corneal dystrophy type I (LCDI), granular corneal dystrophy (CDGG1) and Avellino stromal dystrophy (ASD), all mapped on 5q31, were found to be associated to four different mutations in the beta ig-h3 gene which codify for kerato-epithelin. We identified several cases of RBCD in Sardinia. We reconstructed through genealogical search two eight generation-families, originating from the same village (Arbus), indicating a common ancestor for RBCD in Sardinia. Linkage studies on these families confirmed the association of the disease with the 5q31 region. Sequence analysis of beta ig-h3 gene revealed a trinucleotide deletion in exon 12, corresponding to the loss of F540 in the protein sequence (delta F540). Our data describe a new mutation in the beta ig-h3 gene causing RBCD. This dominant negative mutation is located in the fourth internal repeat of kerato-epithelin which is a protein domain highly conserved across species. This suggests the basic role of this domain in maintaining the proper kerato-epithelin structure which when altered can cause the typical precipitates in the RBCD cornea.
12. A multicenter retrospective study of charcot-marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins (MTMRs)
- Author
-
Nathalie Bonello-Palot, Chiara Pisciotta, Mario Sabatelli, Rita Horvath, Stefano C. Previtali, Alessandro Geroldi, Esra Battaloglu, Julian Blake, André Mégarbané, Raquel Guimarães-Costa, Matilde Laura, Alberto A. Zambon, Angelo Schenone, Lucio Santoro, Sabrina Sacconi, Philippe Latour, Yesim Parman, Michael E. Shy, Chiara Gemelli, Irene Tramacere, Sarah Leonard-Louis, Mounia Bellatache, Nicolas Lévy, Steven S. Scherer, Byung Ok Choi, Aldo Quattrone, S. Attarian, Tatsufumi Murakami, Lois Dankwa, Paola Valentino, David N. Herrmann, Marco Luigetti, Mary M. Reilly, Stefania Magri, Fiore Manganelli, Davide Pareyson, Meriem Tazir, Chelsea Bacon, Guilhem Solé, Alessandra Bolino, Tanya Stojkovic, Giulia Ricci, Pareyson, D., Stojkovic, T., Reilly, M. M., Leonard-Louis, S., Laura, M., Blake, J., Parman, Y., Battaloglu, E., Tazir, M., Bellatache, M., Bonello-Palot, N., Levy, N., Sacconi, S., Guimaraes-Costa, R., Attarian, S., Latour, P., Sole, G., Megarbane, A., Horvath, R., Ricci, G., Choi, B. -O., Schenone, A., Gemelli, C., Geroldi, A., Sabatelli, M., Luigetti, M., Santoro, L., Manganelli, F., Quattrone, A., Valentino, P., Murakami, T., Scherer, S. S., Dankwa, L., Shy, M. E., Bacon, C. J., Herrmann, D. N., Zambon, A., Tramacere, I., Pisciotta, C., Magri, S., Previtali, S. C., Bolino, A., CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Service de Neurologie, CHU Mustapha, 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), 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), CHU Nice, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Filière Neuromusculaire (FILNEMUS), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jérôme Lejeune, CHU Trousseau [APHP], University of Pisa - Università di Pisa, Department of Neuroscience, Ophtalmology and Genetics, Genova, Università cattolica del Sacro Cuore [Roma] (Unicatt), Department of Neuroscience, Catholic University, Roma, University of Naples Federico II, Institute of Bioimaging and Molecular Physiology [Germaneto], National Research Council [Italy] (CNR), Istituto di Ricerche Farmacologiche 'Mario Negri', 20156 Milan, Human Inherited Neuropathies Unit, San Raffaele Scientific Institute-INSPE-Institute for Experimental Neurology, Dulbecco Telethon Institute, San Raffaele Scientific Institute, Bonello-Palot, Nathalie [0000-0002-8657-1271], Previtali, Stefano C [0000-0003-2546-4357], Bolino, Alessandra [0000-0002-8980-4878], Apollo - University of Cambridge Repository, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), and University of Naples Federico II = Università degli studi di Napoli Federico II
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Cord ,Adolescent ,Myotubularin ,Glaucoma ,Disease ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Charcot-Marie-Tooth Disease ,Internal medicine ,medicine ,Humans ,Young adult ,Child ,Loss function ,Retrospective Studies ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,hereditary neuropathies ,Retrospective cohort study ,Middle Aged ,Protein Tyrosine Phosphatases, Non-Receptor ,medicine.disease ,Phenotype ,3. Good health ,Settore MED/26 - NEUROLOGIA ,030104 developmental biology ,Neurology ,Child, Preschool ,Mutation ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
International audience; Objective Charcot-Marie-Tooth (CMT) disease 4B1 and 4B2 (CMT4B1/B2) are characterized by recessive inheritance, early onset, severe course, slowed nerve conduction, and myelin outfoldings. CMT4B3 shows a more heterogeneous phenotype. All are associated with myotubularin-related protein (MTMR) mutations. We conducted a multicenter, retrospective study to better characterize CMT4B. Methods We collected clinical and genetic data from CMT4B subjects in 18 centers using a predefined minimal data set including Medical Research Council (MRC) scores of nine muscle pairs and CMT Neuropathy Score. Results There were 50 patients, 21 of whom never reported before, carrying 44 mutations, of which 21 were novel and six representing novel disease associations of known rare variants. CMT4B1 patients had significantly more-severe disease than CMT4B2, with earlier onset, more-frequent motor milestones delay, wheelchair use, and respiratory involvement as well as worse MRC scores and motor CMT Examination Score components despite younger age at examination. Vocal cord involvement was common in both subtypes, whereas glaucoma occurred in CMT4B2 only. Nerve conduction velocities were similarly slowed in both subtypes. Regression analyses showed that disease severity is significantly associated with age in CMT4B1. Slopes are steeper for CMT4B1, indicating faster disease progression. Almost none of the mutations in the MTMR2 and MTMR13 genes, responsible for CMT4B1 and B2, respectively, influence the correlation between disease severity and age, in agreement with the hypothesis of a complete loss of function of MTMR2/13 proteins for such mutations. Interpretation This is the largest CMT4B series ever reported, demonstrating that CMT4B1 is significantly more severe than CMT4B2, and allowing an estimate of prognosis. ANN NEUROL 2019
- Published
- 2019
13. 'Myocilin Gln368stop mutation and advanced age as risk factors for late-onset primary open-angle glaucoma'
- Author
-
Nicola Orzalesi, Paolo Gasparini, Giuseppina Casu, Luciano Bonomi, Leopoldo Zelante, Mario Pirastu, Andrea Angius, Giuseppe Ghilotti, Patrizia Spinelli, Angela Loi, Antonio Totaro, Gabriella Sole, Angius, A, Spinelli, P, Ghilotti, G, Casu, G, Sole, G, Loi, A, Totaro, A, Zelante, L, Gasparini, Paolo, Orzalesi, N, Pirastu, M, and Bonomi, L.
- Subjects
Male ,medicine.medical_specialty ,genetic structures ,Open angle glaucoma ,DNA Mutational Analysis ,Ocular hypertension ,Glaucoma ,Risk Factors ,Internal medicine ,Ophthalmology ,medicine ,Humans ,Missense mutation ,Age of Onset ,Eye Proteins ,Myocilin ,Aged ,Glycoproteins ,Aged, 80 and over ,business.industry ,Age Factors ,DNA ,Middle Aged ,medicine.disease ,Penetrance ,eye diseases ,Pedigree ,Cytoskeletal Proteins ,Mutation ,Mutation (genetic algorithm) ,Codon, Terminator ,Female ,Ocular Hypertension ,sense organs ,Age of onset ,DNA Probes ,business ,Glaucoma, Open-Angle - Abstract
Juvenile open-angle glaucoma has been found to be associated with molecular defects in the myocilin (MYOC) gene. Most of the defects are missense mutations located in the third exon. The Gln368stop mutation has recently been found in several cases of late-onset primary open-angle glaucoma (POAG).To study the effect of glaucoma risk in a relatively homogeneous genetic population.A clinical study was performed in all living members of a 5-generation family. DNA analysis was performed for studying association with genetic markers and identifying the mutation.We identified the Gln368stop molecular defect in 19 patients with POAG, 5 patients with ocular hypertension, and 22 healthy carriers. We compared affected and unaffected carriers based on age at onset and last examination, respectively. Besides the presence of 3 young patients with POAG (40 years old), the number of glaucomatous patients in the advanced age group increased.The penetrance of glaucoma increases with age in Gln368stop carriers, but some remain unaffected at advanced age and others are affected at an early age. This suggests that additional risk factors are operating within this family, which may be identified by a genome-wide linkage search in this large pedigree.The myocilin Gln368stop mutation shows a good genotype-phenotype correlation and should be investigated in all familiar cases of chronic POAG. This may be important for early diagnosis and periodical checkups of presymptomatic individuals belonging to these families.
- Published
- 2000
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.