Search

Your search keyword '"Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES]"' showing total 11 results
Start Over Descriptor "Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES]"
Sorry, I don't understand your search. ×
11 results on '"Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES]"'

1. Extending the phenotypes associated with <scp> TRIO </scp> gene variants in a cohort of 25 patients and review of the literature

Author

Gabriella Gazdagh, David Hunt, Anna Maria Cueto Gonzalez, Monserrat Pons Rodriguez, Ayeshah Chaudhry, Marcos Madruga, Fleur Vansenne, Deborah Shears, Aurore Curie, Eva‐Lena Stattin, Britt‐Marie Anderlid, Slavica Trajkova, Elena Sukarova Angelovska, Catherine McWilliam, Philip R. Wyatt, Mary O'Driscoll, Giles Atton, Anke K. Bergman, Pia Zacher, Leena D. Mewasingh, Antonio Gonzalez‐Meneses López, Olga Alonso‐Luengo, Htoo A. Wai, Ottilie Rohde, Pauline Boiroux, Anne Debant, Susanne Schmidt, Diana Baralle, Institut Català de la Salut, [Gazdagh G] Wessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, UK. Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. [Hunt D] Wessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, UK. [Cueto Gonzalez AM] Servei de Genètica Clínica i Molecular, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Pons Rodriguez M] Hospital Universitari Son Espases, Palma, Illes Balears, Spain. [Chaudhry A] Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, Ontario, Canada. Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. [Madruga M] Hospital Viamed Santa Angela De la Cruz, Sevilla, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
enfermedades del sistema nervioso::malformaciones del sistema nervioso [ENFERMEDADES], phenotype, Nervous System Diseases::Nervous System Malformations [DISEASES], fenómenos genéticos::variación genética::mutación::mutación de sentido erróneo [FENÓMENOS Y PROCESOS], macrocephaly, Sistema nerviós - Malalties - Aspectes genètics, Fenotip, spectrin, Anomalies cromosòmiques, GEFD, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Genetics, TRIO gene, Malformacions, Genetic Phenomena::Genetic Variation::Mutation::Mutation, Missense [PHENOMENA AND PROCESSES], microcephaly, Medical Genetics, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Genetics (clinical), Medicinsk genetik
Abstract

TRIO gene; Macrocephaly; Phenotype Gen TRIO; Macrocefàlia; Fenotip Gen TRIO; Macrocefalia; Fenotipo The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature. Here, we report an additional 25, previously unreported individuals who possess heterozygous TRIO variants and we review the literature. In addition, functional studies were performed on the c.4394A > G (N1465S) and c.6244-2A > G TRIO variants to provide evidence for their pathogenicity. Variants reported by the current study include missense variants, truncating nonsense variants, and an intragenic deletion. Clinical features were previously described and included developmental delay, learning difficulties, microcephaly, macrocephaly, seizures, behavioral issues (aggression, stereotypies), skeletal problems including short, tapering fingers and scoliosis, dental problems (overcrowding/delayed eruption), and variable facial features. Here, we report clinical features that have not been described previously, including specific structural brain malformations such as abnormalities of the corpus callosum and ventriculomegaly, additional psychological and dental issues along with a more recognizable facial gestalt linked to the specific domains of the TRIO gene and the effect of the variant upon the function of the encoded protein. This current study further strengthens the genotype-to-phenotype correlation that was previously established and extends the range of phenotypes to include structural brain abnormalities, additional skeletal, dental, and psychiatric issues. This work was supported by grants from the Agence Nationale de la Recherche to Anne Debant (ANR-2019 TRIOTISM). Diana Baralle is supported by National Institute for Health Research (NIHR) (RP-2016-07-011) research professorship.

Published
2023
Full Text
View/download PDF

2. Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology

Author

Ferdinand Dhombres, Patricia Morgan, Bimal P. Chaudhari, Isabel Filges, Teresa N. Sparks, Pablo Lapunzina, Tony Roscioli, Umber Agarwal, Shagun Aggarwal, Claire Beneteau, Pilar Cacheiro, Leigh C. Carmody, Sophie Collardeau‐Frachon, Esther A. Dempsey, Andreas Dufke, Michael Henri Duyzend, Mirna el Ghosh, Jessica L. Giordano, Ragnhild Glad, Ieva Grinfelde, Dominic G. Iliescu, Markus S. Ladewig, Monica C. Munoz‐Torres, Marzia Pollazzon, Francesca Clementina Radio, Carlota Rodo, Raquel Gouveia Silva, Damian Smedley, Jagadish Chandrabose Sundaramurthi, Sabrina Toro, Irene Valenzuela, Nicole A. Vasilevsky, Ronald J. Wapner, Roni Zemet, Melissa A Haendel, Peter N. Robinson, Institut Català de la Salut, [Dhombres F] Sorbonne University, GRC26, INSERM, Limics, Armand Trousseau Hospital, Fetal Medicine Department, APHP, Paris, France. [Morgan P] American College of Medical Genetics and Genomics, Newborn Screening Translational Research Network, Bethesda, USA. [Chaudhari BP] Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, USA. [Filges I] University Hospital Basel and University of Basel, Medical Genetics, Basel, Switzerland. [Sparks TN] Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, California, USA. [Lapunzina P] CIBERER and Hospital Universitario La Paz, INGEMM-Institute of Medical and Molecular Genetics, Madrid, Spain. [Rodo C] Grup de Recerca en Medicina Materna i Fetal, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Valenzuela I] Àrea de Genètica Clínica i Molecular, Vall d'Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, American College of Medical Genetics and Genomics [Bethesda, MD, USA] (ACM2G), Nationwide Children's Hospital, University Hospital Basel [Basel], University of Basel (Unibas), University of California [San Francisco] (UC San Francisco), University of California (UC), CIBER de Enfermedades Raras (CIBERER), Hospital Universitario La Paz, University of New South Wales [Canberra Campus] (UNSW), Liverpool Women's NHS Foundation Trust, Nizam's Institute of Medical Sciences (NIMS), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Queen Mary University of London (QMUL), The Jackson Laboratory [Bar Harbor] (JAX), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Société Française de Foetopathologie [Paris] (SOFFOET), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), St George's, University of London, University of Tübingen, Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Columbia University Irving Medical Center (CUIMC), University Hospital of North Norway [Tromsø] (UNN), Children's Clinical University Hospital [Riga, Latvia] (CCUH), University of Medicine and Pharmacy of Craiova, Saarland University Hospital (UKS), University of Colorado Anschutz [Aurora], AUSL di Reggio Emilia Istituto di Ricerca a Carattere Clinico Scientifico [Reggio Emilia, Italie], IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Vall d'Hebron University Hospital [Barcelona], Hospital de Santa Maria [Lisboa], Centro Hospitalar Universitário Lisboa Norte [Lisbon, Portugal] (CHULN), Baylor College of Medicine (BCM), Baylor University, and CarMeN, laboratoire

Subjects
prenatal phenotyping, [SDV]Life Sciences [q-bio], Placenta, Clinical Sciences, Diagnòstic prenatal, fetal pathology, Reproductive health and childbirth, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras [ENFERMEDADES], Rare Diseases, Pregnancy, Clinical Research, Exome Sequencing, Genetics, Humans, Genetics (clinical), Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Obstetrical and Gynecological::Prenatal Diagnosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Pediatric, Genetics & Heredity, diagnóstico::técnicas y procedimientos diagnósticos::técnicas diagnósticas obstétricas y ginecológicas::diagnóstico prenatal [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], screening and diagnosis, prenatal diagnosis, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases [DISEASES], Prevention, Human Genome, Infant, Newborn, Computational Biology, Infant, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, 4.1 Discovery and preclinical testing of markers and technologies, [SDV] Life Sciences [q-bio], Fenotip, Detection, Phenotype, Good Health and Well Being, Neurological, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], GA4GH Phenopacket, Congenital Structural Anomalies, Female, Hpo, HPO, Malalties rares, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], human phenotype ontology
Abstract

Human phenotype ontology; Prenatal diagnosis; Prenatal phenotyping Ontología del fenotipo humano; Diagnóstico prenatal; Fenotipado prenatal Ontologia del fenotip humà; Diagnòstic prenatal; Fenotipat prenatal Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care. European Commission; National Human Genome Research Institute; NIH Office of the Director; The European Union's EIT-Health Innovation Program bp2020-2022, Grant/Award Numbers: #211015, #20062; NIH Office of the Director (OD), the European Union's Horizon 2020 research and innovation program, Grant/Award Number: 779257; NHGRI, Grant/Award Numbers: 2R24OD011883-05A1, 1U24HG011449-01A1

Published
2022
Full Text
View/download PDF

3. A Novel Intragenic Duplication in the HDAC8 Gene Underlying a Case of Cornelia de Lange Syndrome

Author

Cristina Lucia-Campos, Irene Valenzuela, Ana Latorre-Pellicer, David Ros-Pardo, Marta Gil-Salvador, María Arnedo, Beatriz Puisac, Neus Castells, Alberto Plaja, Anna Tenes, Ivon Cuscó, Laura Trujillano, Feliciano J. Ramos, Eduardo F. Tizzano, Paulino Gómez-Puertas, Juan Pié, Institut Català de la Salut, [Lucia-Campos C, Latorre-Pellicer A, Gil-Salvador M, Arnedo M] Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, Universidad de Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain. [Valenzuela I, Castells N, Plaja A, Tenes A, Trujillano L, Tizzano EF] Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Medicina Genètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Ros-Pardo D] Centro de Biología Molecular Severo Ochoa, CBMSO (CSIC-UAM), Molecular Modeling Group, Madrid, Spain. [Cuscó I] Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Medicina Genètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Department of Genetics, Hospital Sant Pau, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Discapacitat intel·lectual - Aspectes genètics, Otros calificadores::Otros calificadores::/genética [Otros calificadores], intragenic duplication, enfermedades del sistema nervioso::manifestaciones neurológicas::manifestaciones neuroconductuales::discapacidad intelectual::síndrome de De Lange [ENFERMEDADES], Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn [DISEASES], Cornelia de Lange syndrome, Fenotip, genetic diagnosis, HDAC8, Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability::De Lange Syndrome [DISEASES], Other subheadings::Other subheadings::/genetics [Other subheadings], Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Genetics, array CGH, genetic disorder, copy number variants, Malalties congènites, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas [ENFERMEDADES], fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Genetics (clinical)
Abstract

Cornelia de Lange syndrome; Genetic disorder; Intragenic duplication Síndrome de Cornelia de Lange; Trastorno genético; Duplicación intragénica Síndrome de Cornelia de Lange; Trastorn genètic; Duplicació intragènica Cornelia de Lange syndrome (CdLS) is a multisystemic genetic disorder characterized by distinctive facial features, growth retardation, and intellectual disability, as well as various systemic conditions. It is caused by genetic variants in genes related to the cohesin complex. Single-nucleotide variations are the best-known genetic cause of CdLS; however, copy number variants (CNVs) clearly underlie a substantial proportion of cases of the syndrome. The NIPBL gene was thought to be the locus within which clinically relevant CNVs contributed to CdLS. However, in the last few years, pathogenic CNVs have been identified in other genes such as HDAC8, RAD21, and SMC1A. Here, we studied an affected girl presenting with a classic CdLS phenotype heterozygous for a de novo ~32 kbp intragenic duplication affecting exon 10 of HDAC8. Molecular analyses revealed an alteration in the physiological splicing that included a 96 bp insertion between exons 9 and 10 of the main transcript of HDAC8. The aberrant transcript was predicted to generate a truncated protein whose accessibility to the active center was restricted, showing reduced ease of substrate entry into the mutated enzyme. Lastly, we conclude that the duplication is responsible for the patient’s phenotype, highlighting the contribution of CNVs as a molecular cause underlying CdLS. This work was supported by the Spanish Ministry of Health-ISCIII Fondo de Investigación Sanitaria (FIS) (Ref. PI19/01860, to F.J.R. and J.P.) and Diputación General de Aragón-FEDER: European Social Fund (Grupo de Referencia B32_17R/B32_20R, to J.P.). A.L.-P. is supported by a “Juan de la Cierva-Incorporación” postdoctoral grant from MICIU (Spanish Ministry of Science and Universities), M.G.-S. is supported by a Predoctoral Fellowship from the Diputación General de Aragón, and C.L.-C. is supported by a Predoctoral Fellowship from the MH-ISCIII. This work was also supported by Spanish government grants RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE) and DTS20-00024 (ISCIII) to P.G.-P., as well as funds from the European JPIAMR network “EPIC-Alliance” to P.G.-P. The computational support of the “Centro de Computación Científica CCC-UAM” is gratefully recognized. This work was also partially supported by Spanish Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-funded with ERDF funds, Grant No. FIS PI20/01767) to A.P. and by Spanish Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-funded with ERDF funds, Grant No. FIS PI18/000687 to E.F.T.

Published
2022

4. The LEGACy study: a European and Latin American consortium to identify risk factors and molecular phenotypes in gastric cancer to improve prevention strategies and personalized clinical decision making globally

Author

Tessa Suzanne, van Schooten, Sarah, Derks, Elena, Jiménez-Martí, Fatima, Carneiro, Ceu, Figueiredo, Erika, Ruiz, Maria, Alsina, Cristina, Molero, Marcelo, Garrido, Arnoldo, Riquelme, Carmelo, Caballero, Eva, Lezcano, Juan Manuel, O'Connor, Federico, Esteso, Judith, Farrés, José Manuel, Mas, Florian, Lordick, Jeannette, Vogt, Antonella, Cardone, Charis, Girvalaki, Andrés, Cervantes, Tania, Fleitas, VU University medical center, Internal medicine, CCA - Cancer biology and immunology, Institut Català de la Salut, [van Schooten TS, Derks S] Amsterdam UMC location VUMC, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands. Oncode Institute, Utrecht, The Netherlands. [Jiménez-Martí E] Instituto Investigación Sanitaria INCLIVA (INCLIVA), CIBERONC, Medical Oncology Department, Hospital Clínico Universitario de Valencia, Universitat de Valencia, Valencia, Spain. [Carneiro F, Figueiredo C] Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP)/Institute of Research and Innovation in Health (i3S). Faculty of Medicine, University of Porto, Porto, Portugal. [Ruiz E] Instituto Nacional de Cancerología (INCAN), Translational Medicine Laboratory & GI Cancer Department, Mexico City, Mexico. [Alsina M, Molero C] Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias gástricas [ENFERMEDADES], Cancer Research, Prevention, Clinical Decision-Making, diagnóstico::toma de decisiones clínicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Fenotip, Latin America, Phenotype, Oncology, Tumor microenvironment, Risk Factors, Stomach Neoplasms, Case-Control Studies, Decisió, Presa de, Diagnosis::Clinical Decision-Making [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Genetics, Humans, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms [DISEASES], Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Gastric cancer, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Estómac - Càncer - Factors de risc
Abstract

Background Gastric Cancer (GC) is the fourth most deadly cancer worldwide. Enhanced understanding of its key epidemiological and molecular drivers is urgently needed to lower the incidence and improve outcomes. Furthermore, tumor biology in European (EU) and Latin American (LATAM) countries is understudied. The LEGACy study is a Horizon 2020 funded multi-institutional research approach to 1) detail the epidemiological features including risk factors of GC in current time and 2) develop cost-effective methods to identify and integrate biological biomarkers needed to guide diagnostic and therapeutic approaches with the aim of filling the knowledge gap on GC in these areas. Methods This observational study has three parts that are conducted in parallel during 2019–2023 across recruiting centers from four EU and four LATAM countries: Part 1) A case-control study (800 cases and 800 controls) using questionnaires on candidate risk factors for GC, which will be correlated with clinical, demographic and epidemiological parameters. Part 2) A case-control tissue sampling study (400 cases and 400 controls) using proteome, genome, microbiome and immune analyses to characterize advanced (stage III and IV) GC. Patients in this part of the study will be followed over time to observe clinical outcomes. The first half of samples will be used as training cohort to identify the most relevant risk factors and biomarkers, which will be selected to propose cost-effective diagnostic and predictive methods that will be validated with the second half of samples. Part 3) An educational study, as part of our prevention strategy (subjects recruited from the general public) to test and disseminate knowledge on GC risk factors and symptoms by a questionnaire and informative video. Patients could be recruited for more than one of the three LEGACy studies. Discussion The LEGACy study aims to generate novel, in-depth knowledge on the tumor biological characteristics through integrating epidemiological, multi-omics and clinical data from GC patients at an EU-LATAM partnership. During the study, cost-effective panels with potential use in clinical decision making will be developed and validated. Trial registration ClinicalTrials.gov Identifiers: Part 1: NCT03957031. Part 2: NCT04015466. Part 3: NCT04019808.

Published
2022
Full Text
View/download PDF

5. Characterising the axial phenotype of psoriatic arthritis: a study comparing axial psoriatic arthritis and ankylosing spondylitis with psoriasis from the REGISPONSER registry

Author

Xabier Michelena, Clementina López-Medina, Alba Erra, Xavier Juanola, Pilar Font-Ugalde, Eduardo Collantes, Helena Marzo-Ortega, Institut Català de la Salut, [Michelena X] Servei de Reumatologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. NIHR Leeds BRC, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. [López-Medina C, Font-Ugalde P, Collantes E] Maimónides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain. Rheumatology, Reina Sofía University Hospital, Córdoba, Spain. [Erra A] Servei de Reumatologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Juanola X] Rheumatology, Hospital Universitari de Bellvitge, Barcelona, Spain. [Marzo-Ortega H] NIHR Leeds BRC, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Psoriasi, Musculoskeletal Diseases::Bone Diseases::Spinal Diseases::Spondylitis::Spondylarthritis::Spondylarthropathies::Spondylitis, Ankylosing [DISEASES], Artritis psoriàsica, Espondiloartritis anquilosant, Artritis, Musculoskeletal Diseases::Bone Diseases::Spinal Diseases::Spondylitis::Spondylarthritis::Spondylarthropathies::Arthritis, Psoriatic [DISEASES], Epidemiology, Arthritis, enfermedades musculoesqueléticas::enfermedades óseas::enfermedades de la columna vertebral::espondilitis::espondiloartritis::espondiloartropatías::espondilitis anquilosante [ENFERMEDADES], Immunology, Artritis reumatoide, Fenotip, Rheumatology, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Psoriasis, Immunology and Allergy, Epidemiologia, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], enfermedades musculoesqueléticas::enfermedades óseas::enfermedades de la columna vertebral::espondilitis::espondiloartritis::espondiloartropatías::artritis psoriásica [ENFERMEDADES], Ankylosing spondylitis
Abstract

Espondilitis anquilosante; Artritis; Epidemiología Espondilitis anquilosant; Artritis; Epidemiologia Ankylosing spondylitis; Arthritis; Epidemiology Aims To explore the clinical and radiographical characteristics of axial psoriatic arthritis (PsA) and to compare it with ankylosing spondylitis (AS) with psoriasis. Methods Cross-sectional study from the national multicentre registry REGISPONSER where participants fulfilled the European Spondyloarthropathy Study Group spondyloarthritis criteria at entry. Clinical, laboratory and radiographical characteristics between patients classified as axial PsA and AS with psoriasis by their rheumatologist are compared according to HLA-B27 status. Results Of 2367 patients on REGISPONSER, n=405 had PsA, of whom 27% (n=109) had axial involvement as per the treating rheumatologist. 30% (n=26/86) of axial PsA were HLA-B27 positive. In the AS group, 9% (127/1422) had a history of psoriasis and were more frequently male, with longer diagnostic delay and more anterior uveitis than those with axial PsA who had more peripheral involvement and nail disease. Patients with HLA-B27-negative axial PsA reported less inflammatory pain and structural damage compared with AS with psoriasis. By contrast, HLA-B27-positive axial PsA shared clinical characteristics similar to AS and psoriasis although with a lower BASRI score. In the multivariable analysis, patients with AS and psoriasis were independently associated with HLA-B27 positivity (OR 3.34, 95% CI 1.42 to 7.85) and lumbar structural damage scored by BASRI (OR 2.14, 95% CI 1.4 to 3.19). Conclusion The more prevalent axial PsA phenotype is predominantly HLA-B27 negative and presents different clinical and radiological manifestations when compared with AS with psoriasis. There is great heterogeneity in what rheumatologists consider axial PsA from a clinical and imaging perspective, highlighting the need for research into possible genetic drivers and a consensus definition. HM-O is supported by the National Institute for Health Research Leeds Biomedical Research Centre. The REGISPONSER registry is funded by an unrestricted grant from the Spanish Society for Rheumatology. There was no specific funding for the current analysis.

Published
2022
Full Text
View/download PDF

6. Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Author

Dolores Martínez-Rubio, Isabel Hinarejos, Paula Sancho, Nerea Gorría-Redondo, Raquel Bernadó-Fonz, Cristina Tello, Clara Marco-Marín, Itxaso Martí-Carrera, María Jesús Martínez-González, Ainhoa García-Ribes, Raquel Baviera-Muñoz, Isabel Sastre-Bataller, Irene Martínez-Torres, Anna Duat-Rodríguez, Patrícia Janeiro, Esther Moreno, Leticia Pías-Peleteiro, Mar O’Callaghan Gordo, Ángeles Ruiz-Gómez, Esteban Muñoz, Maria Josep Martí, Ana Sánchez-Monteagudo, Candela Fuster, Amparo Andrés-Bordería, Roser Maria Pons, Silvia Jesús-Maestre, Pablo Mir, Vincenzo Lupo, Belén Pérez-Dueñas, Alejandra Darling, Sergio Aguilera-Albesa, Carmen Espinós, Institut Català de la Salut, [Martínez-Rubio D, Hinarejos I] Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. Joint Unit CIPF-IIS La Fe Rare Diseases, Valencia, Spain. [Sancho P, Tello C] Rare Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. [Gorría-Redondo N, Bernadó-Fonz R] Paediatric Neurology Unit, Department of Paediatrics, Hospital Universitario de Navarra, Navarrabiomed, Pamplona, Spain. [Pérez-Dueñas B] Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Instituto de Salud Carlos III, European Commission, Fundació La Marató de TV3, Generalitat Valenciana, Ministerio de Educación, Cultura y Deporte (España), Fundació per Amor a L'Art, Marco-Marín, Clara [0000-0002-8813-3515], and Marco-Marín, Clara

Subjects
Iron, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Kinesins, Catalysis, Atàxia - Aspectes genètics, Inorganic Chemistry, cerebellar atrophy, gene panel, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, movement disorders, ataxia, neurodegeneration with brain iron accumulation (NBIA), exome sequencing, Physical and Theoretical Chemistry, Molecular Biology, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Spectroscopy, Movement Disorders, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, Brain, Neurodegenerative Diseases, General Medicine, Computer Science Applications, Fenotip, Phosphotransferases (Alcohol Group Acceptor), Anomalies cromosòmiques, Phenotype, enfermedades del sistema nervioso::manifestaciones neurológicas::discinesias::ataxia [ENFERMEDADES], Mutation, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Ataxia, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Nervous System Diseases::Neurologic Manifestations::Dyskinesias::Ataxia [DISEASES]
Abstract

26 páginas, 4 figuras, 3 tablas, Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype., This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D+I Plan co-funded with European Regional Development Funds (ERDF) [Grants PI18/00147 and PI21/00103 to CE]; the Fundació La Marató TV3 [Grants 20143130 and 20143131 to BPD and CE]; and by the Generalitat Valenciana [Grant PROMETEO/2018/135 to CE]. Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014–2020). PS had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. IH has a PFIS-PhD fellowship [FI19/00072]. ASM has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA)

Published
2022
Full Text
View/download PDF

7. When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD

Author

Alba Rojano-Toimil, Jesús Rivera-Esteban, Ramiro Manzano-Nuñez, Juan Bañares, David Martinez Selva, Pablo Gabriel-Medina, Roser Ferrer, Juan M Pericàs, Andreea Ciudin, Institut Català de la Salut, [Rojano-Toimil A] Servei d’Endocrinologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Rivera-Esteban J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Hepàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Manzano-Nuñez R, Bañares J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat Hepàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Martinez Selva D] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Spanish Network of Biomedical Research Centers, Diabetes and Metabolic Associated Disorders (CIBERdem), Madrid, Spain. [Gabriel-Medina P] Servei de Bioquímica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ferrer R] Servei de Bioquímica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pericàs JM] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat Hepàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Network of Biomedical Research Centers, Liver and Digestive Diseases (CIBERehd), Madrid, Spain. [Ciudin A] Servei d’Endocrinologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Network of Biomedical Research Centers, Diabetes and Metabolic Associated Disorders (CIBERdem), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Fenotip, enfermedades del sistema endocrino::diabetes mellitus::diabetes mellitus tipo II [ENFERMEDADES], enfermedades del sistema digestivo::enfermedades hepáticas::hígado graso::esteatosis hepática no alcohólica [ENFERMEDADES], Esteatosi hepàtica - Diagnòstic, Other subheadings::/diagnosis [Other subheadings], Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Otros calificadores::/diagnóstico [Otros calificadores], Digestive System Diseases::Liver Diseases::Fatty Liver::Non-alcoholic Fatty Liver Disease [DISEASES], Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2 [DISEASES], General Medicine, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Diabetis no-insulinodependent
Abstract

MODY diabetes; Liver fibrosis; Type 2 diabetes Diabetes MODY; Fibrosis hepática; Diabetes tipo 2 Diabetis MODY; Fibrosi hepàtica; Diabetis tipus 2 Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.

Published
2022
Full Text
View/download PDF

8. Is asthma a risk factor for COVID-19? Are phenotypes important?

Author

Christian Romero-Mesones, Florencia Pilia, María Jesús Cruz, Iñigo Ojanguren, Xavier Muñoz, Institut Català de la Salut, [Muñoz X] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Pilia F, Romero-Mesones C] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ojanguren I, Cruz MJ] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, lcsh:Medicine, COVID-19 (Malaltia), 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Research Letter, medicine, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 030212 general & internal medicine, Risk factor, Asma, Asthma, business.industry, lcsh:R, virus diseases, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Respiratory Tract Diseases::Bronchial Diseases::Asthma [DISEASES], medicine.disease, Phenotype, respiratory tract diseases, Fenotip, 030228 respiratory system, Immunology, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], enfermedades respiratorias::enfermedades bronquiales::asma [ENFERMEDADES], business, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS]
Abstract

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Infeccions respiratòries i tuberculosi; Asma i al·lèrgia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; COVID-19; Infecciones respiratorias y tuberculosis; Asma y alergia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Respiratory infections and tuberculosis; Asthma and allergy These results reaffirm the idea that asthma does not appear to be a risk factor for the development of #COVID19. However, most of the asthma patients in this study had a non-T2 phenotype.

Published
2021

9. Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

Author

Bertrand Isidor, Ruth Armstrong, Thabo M. Yates, Susan M. White, Ruth Richardson, Solveig Heide, Katherine B. Burke, Tjitske Kleefstra, Marie Vincent, Meena Balasubramanian, Maria Irene Valenzuela Palafoll, Sébastien Küry, Rolph Pfundt, Ruth Newbury-Ecob, Sahar Mansour, Wendy K. Chung, Caroline Nava, Sofia Douzgou, Erika Leenders, Annachiara De Sandre-Giovannoli, Saba Sharif, Andrew E. Fry, Helen Stewart, Nicola K. Ragge, Alexander J. M. Dingemans, Pradeep C. Vasudevan, Alison Foster, Sahar Elouej, Shadi Albaba, François-Guillaume Debray, Boris Keren, Serwet Demirdas, Francis H. Sansbury, Thomas Scheffner, Arie van Haeringen, Alice S. Brooks, Meyke Schouten, Helen Cox, Kate Wilson, Sheffield Children's NHS Foundation Trust, University of Sheffield [Sheffield], Radboud University Medical Center [Nijmegen], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Birmingham Children’s Hospital, Manchester University NHS Foundation Trust (MFT), University of Manchester [Manchester], Addenbrooke's Hospital, Cambridge University NHS Trust, University Hospital of Wales, Oxford Brookes University, 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), 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)-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), St. George’s Hospital University, Oxford University Hospitals NHS Foundation Trust, Partenaires INRAE, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Leiden University Medical Center (LUMC), Reutlingen University, Centre Hospitalier Universitaire de Liège (CHU-Liège), Murdoch Children's Research Institute (MCRI), University of Melbourne, Vall d'Hebron University Hospital [Barcelona], University Hospitals Bristol, Clinical Genetics, Institut Català de la Salut, [Balasubramanian M] Sheffield Clinical Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. Academic Unit of Child Health, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK. [Dingemans AJM] Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. [Albaba S] Sheffield Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. [Richardson R] Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Trust, Newcastle, UK. [Yates TM] Sheffield Clinical Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. [Cox H] West Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, UK. [Palafoll MIV] Servei de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Medicina Genètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, University Hospital of Wales (UHW), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and Universiteit Leiden

Subjects
Male, Pediatrics, Genetic testing, Developmental Disabilities, Craniofacial Abnormalities, Intellectual disability, Missense mutation, Child, Genetics (clinical), trastornos mentales::trastornos del desarrollo neurológico::discapacidades del desarrollo [PSIQUIATRÍA Y PSICOLOGÍA], 0303 health sciences, Otros calificadores::Otros calificadores::/genética [Otros calificadores], 030305 genetics & heredity, Cognition, Syndrome, Autism spectrum disorders, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hypotonia, 3. Good health, Fenotip, Sin3 Histone Deacetylase and Corepressor Complex, Phenotype, Autism spectrum disorder, Child, Preschool, Cohort, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Trastorns del desenvolupament - Aspectes genètics, Infants, medicine.medical_specialty, Adolescent, personas::Grupos de Edad::niño [DENOMINACIONES DE GRUPOS], Article, 03 medical and health sciences, Mental Disorders::Neurodevelopmental Disorders::Developmental Disabilities [PSYCHIATRY AND PSYCHOLOGY], Intellectual Disability, Genetics, medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Attention deficit hyperactivity disorder, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Infant, Persons::Age Groups::Child [NAMED GROUPS], medicine.disease, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Autism, business, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS]
Abstract

Trastornos del espectro autista; Prueba genética Trastorns de l'espectre autista; Prova genètica Autism spectrum disorders; Genetic testing Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12. Funding for the project was provided by the Wellcome Trust and by grants from the Netherlands Organization for Health Research and Development (ZonMw grant 91718310 and the Dutch Scientific Organization (NWO, grant NWA 1160.18.320). WKC is supported by grants from SFARI and the JPB Foundation

Published
2021
Full Text
View/download PDF

10. Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Author

Garcia D, Rios L, Fonticoba T, Bartolome C, Roca L, Painceiras M, Miro C, Canfield H, Jesus S, Aguilar M, Pastor P, Cosgaya M, Caldentey J, Caballol N, Legarda I, Vara J, Cabo I, Manzanares L, Aramburu I, Rivera M, Mayordomo V, Nogueira V, Puente V, Dotor J, Borrue C, Vila B, Sauco M, Vela L, Escalante S, Cubo E, Padilla F, Castrillo J, Alonso P, Losada M, Ariztegui N, Gaston I, Kulisevsky J, Estrada M, Seijo M, Martinez J, Valero C, Kurtis M, de Fabregues O, Ardura J, Redondo R, Ordas C, Diaz L, McAfee D, Martinez-Martin P, Mir P, COPPADIS Study Grp, Instituto de Salud Carlos III, Takeda Pharmaceutical Company, International Parkinson and Movement Disorder Society, AbbVie Pharmaceuticals, Abbott Laboratories, Allergan Foundation, BIAL Foundation, Merz Pharma, UCB Pharma, Zambon, Ministerio de Economía y Competitividad (España), European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Jacques and Gloria Gossweiler Foundation, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Institut Català de la Salut, [Santos-García D, Naya Rios L, Cores Bartolomé C, García Roca L, Feal Painceiras M, Martínez Miró C] Complejo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain. [de Deus Fonticoba T, Canfield H] Complejo Hospitalario Universitario de Ferrol (CHUF), A Coruña, Spain. [Jesús S, Mir P] Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain. Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Aguilar M, Pastor P] Hospital Universitari Mutua de Terrassa, Terrassa , Spain. [Cosgaya M] Hospital Clínic de Barcelona, Barcelona, Spain. [García-Caldentey J] Centro Neurológico Oms, Palma de Mallorca, Spain. [Caballol N] Consorci Sanitari Integral, Hospital Moisés Broggi, Barcelona, Spain. [Legarda I] Hospital Universitari Son Espases, Palma de Mallorca, Spain. [Hernández-Vara J, de Fábregues O] Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Cabo López I, Seijo M] Complexo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain. [López Manzanares L] Hospital Universitario La Princesa, Madrid, Spain. [González Aramburu I] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Ávila Rivera MA] Consorci Sanitari Integral, Hospital General de L'Hospitalet, L'Hospitalet de Llobregat, Spain. [Gómez-Mayordomo V] Hospital Universitario Clínico San Carlos, Madrid, Spain. [Nogueira V] Hospital Da Costa, Burela, Lugo, Spain. [Puente V] Hospital del Mar, Barcelona, Spain. [Dotor J] Hospital Universitario Virgen Macarena, Sevilla, Spain. [Borrué C] Hospital Infanta Sofía, Madrid, Spain. [Solano Vila B] Institut d'Assistència Sanitària (IAS), Institut Català de la Salut (ICS), Salt, Spain. [Álvarez Sauco M] Hospital General Universitario de Elche, Elche, Spain. [Vela-Desojo L] Fundación Hospital de Alcorcón, Madrid, Spain. [Escalante S] Hospital de Tortosa Verge de la Cinta (HTVC), Tortosa, Spain. [Cubo E] Complejo Asistencial Universitario de Burgos, Burgos, Spain. [Carrillo-Padilla F] Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain. [Martínez Castrillo JC] Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain. [Sánchez Alonso P] Hospital Universitario Puerta de Hierro, Madrid, Spain. [Alonso Losada MG] Hospital Álvaro Cunqueiro, Complexo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain. [López-Ariztegui N] Complejo Hospitalario de Toledo, Toledo, Spain. [Gastón I] Complejo Hospitalario de Navarra, Pamplona, Spain. [Kulisevsky J] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Hospital de Sant Pau, Barcelona, Spain. [Blázquez Estrada M] Hospital Universitario Central de Asturias, Oviedo, Spain. [Ruiz-Martínez J] Hospital Universitario Donostia, San Sebastián, Spain. [Valero C] Hospital Arnau de Vilanova, València, Spain. [Kurtis M] Hospital Ruber Internacional, Madrid, Spain. [González Ardura J] Hospital de Cabueñes, Gijón, Spain. [Alonso Redondo R] Universitario Lucus Augusti (HULA), Lugo, Spain. [Ordás C] Hospital Rey Juan Carlos, Madrid, Spain. [López Díaz LM] Complexo Hospitalario Universitario de Ourense (CHUO), Ourense, Spain. [McAfee D] University of Maryland School of Medicine, Baltimore, USA. [Martinez-Martin P] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain, and Institut d'Assistència Sanitària

Subjects
enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::trastornos del movimiento::trastornos parkinsonianos::enfermedades del sistema nervioso::enfermedad de Parkinson [ENFERMEDADES], Medicine (General), changes, motor, Parkinson’s disease, phenotype, PIGD, Tremor, endocrine system diseases, genetic structures, Parkinson's disease, Clinical Biochemistry, Tremolor, Nervous System Diseases::Central Nervous System Diseases::Nervous System Diseases::Central Nervous System Diseases::Movement Disorders::Parkinsonian Disorders::Nervous System Diseases::Parkinson Disease [DISEASES], enfermedades del sistema nervioso::manifestaciones neurológicas::discinesias::temblor [ENFERMEDADES], Article, eye diseases, Fenotip, R5-920, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Parkinson, Malaltia de, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Dyskinesias::Tremor [DISEASES]
Abstract

[Background and objective] Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it., [Patients and Methods] PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls., [Results] The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716)., [Conclusions] Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity., Martínez-Martin P. has received honoraria from National School of Public Health (ISCIII), Editori-al Viguera and Takeda Pharmaceuticals for lecturing in courses, and from the International Parkinson and Movement Disorder Society (MDS) for management of the Program on Rating Scales. Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575], co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [ PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña.

Published
2021

11. A PI*MS is not always a PI*MS. An example of when genotyping for alpha-1 antitrypsin deficiency is necessary

Author

M. Miravitlles, T. Martín, S.T. Furtado, Institut Català de la Salut, [Martín T, Furtado ST] Pneumology Department, Hospital Beatriz Ângelo, Loures, Portugal. [Miravitlles M] Servei de Pneumologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Pulmonary and Respiratory Medicine, Alpha 1-antitrypsin deficiency, Genotype, business.industry, Otros calificadores::Otros calificadores::/genética [Otros calificadores], fenómenos genéticos::genotipo [FENÓMENOS Y PROCESOS], medicine.disease, Fenotip, Genetic Phenomena::Genotype [PHENOMENA AND PROCESSES], Phenotype, enfermedades respiratorias::enfermedades pulmonares::deficiencia de alfa 1-antitripsina [ENFERMEDADES], alpha 1-Antitrypsin Deficiency, Immunology, Pi, medicine, Alfa 1-antitripsina - Aspectes genètics, Other subheadings::Other subheadings::/genetics [Other subheadings], Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Humans, Respiratory Tract Diseases::Lung Diseases::alpha 1-Antitrypsin Deficiency [DISEASES], Genotip, business, Genotyping, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS]
Abstract

Serum glycoprotein; Hereditary disorders Glicoproteïna sèrica; Trastorns hereditaris Glicoproteína sérica; Trastornos hereditarios

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results