33 results match your criteria: "Swiss Institute of Genomic Medicine[Affiliation]"
J Med Genet
November 2024
Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Introduction: Hypomyelinating leukodystrophies are a group of genetic disorders, characterised by severe permanent myelin deficiency. Their clinical features include developmental delay with or without neuroregression, nystagmus, central hypotonia, progressing to spasticity and ataxia. encodes the HSP60 chaperonin protein, mediating ATP-dependent folding of imported proteins in the mitochondrial matrix.
View Article and Find Full Text PDFKlin Monbl Augenheilkd
April 2024
Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland.
Genet Med
September 2023
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. Electronic address:
Purpose: 5-methylcytosine RNA modifications are driven by NSUN methyltransferases. Although variants in NSUN2 and NSUN3 were associated with neurodevelopmental diseases, the physiological role of NSUN6 modifications on transfer RNAs and messenger RNAs remained elusive.
Methods: We combined exome sequencing of consanguineous families with functional characterization to identify a new neurodevelopmental disorder gene.
HGG Adv
July 2023
Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX, USA.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants.
View Article and Find Full Text PDFPediatr Allergy Immunol
April 2023
Unit of Immunology and Vaccinology, Division of General Paediatrics, Department of Paediatrics, Gynaecology and Obstetrics, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
Nat Commun
April 2023
Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland.
Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown.
View Article and Find Full Text PDFAm J Hum Genet
March 2023
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva 1211, Switzerland; Medigenome, Swiss Institute of Genomic Medicine, 1207 Geneva, Switzerland. Electronic address:
Telomere maintenance 2 (TELO2), Tel2 interacting protein 2 (TTI2), and Tel2 interacting protein 1 (TTI1) are the three components of the conserved Triple T (TTT) complex that modulates activity of phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including mTOR, ATM, and ATR, by regulating the assembly of mTOR complex 1 (mTORC1). The TTT complex is essential for the expression, maturation, and stability of ATM and ATR in response to DNA damage. TELO2- and TTI2-related bi-allelic autosomal-recessive (AR) encephalopathies have been described in individuals with moderate to severe intellectual disability (ID), short stature, postnatal microcephaly, and a movement disorder (in the case of variants within TELO2).
View Article and Find Full Text PDFAm J Med Genet A
January 2023
Service de médecine génomique des maladies rares, Hôpital Necker-Enfants Malades (AP-HP centre), Paris, France.
Developmental abnormalities provide a unique opportunity to seek for the molecular mechanisms underlying human organogenesis. Esophageal development remains incompletely understood and elucidating causes for esophageal atresia (EA) in humans would contribute to achieve a better comprehension. Prenatal detection, syndromic classification, molecular diagnosis, and prognostic factors in EA are challenging.
View Article and Find Full Text PDFGenet Med
December 2022
Department of Human Genetics, KU Leuven, Leuven, Belgium; Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium. Electronic address:
Purpose: KLHL20 is part of a CUL3-RING E3 ubiquitin ligase involved in protein ubiquitination. KLHL20 functions as the substrate adaptor that recognizes substrates and mediates the transfer of ubiquitin to the substrates. Although KLHL20 regulates neurite outgrowth and synaptic development in animal models, a role in human neurodevelopment has not yet been described.
View Article and Find Full Text PDFAm J Hum Genet
October 2022
Medigenome, Swiss Institute of Genomic Medicine, 1207 Geneva, Switzerland. Electronic address:
GABA receptors are obligatory heterodimers responsible for prolonged neuronal inhibition in the central nervous system. The two receptor subunits are encoded by GABBR1 and GABBR2. Variants in GABBR2 have been associated with a Rett-like phenotype (MIM: 617903), epileptic encephalopathy (MIM: 617904), and milder forms of developmental delay with absence epilepsy.
View Article and Find Full Text PDFGenet Med
September 2022
Nantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Purpose: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown.
Method: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID).
Results: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.
Genet Med
July 2022
Center for Medical Genetics, Faculty of Medicine and Health Sciences, Antwerp University Hospital, University of Antwerp, Edegem, Belgium; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address:
Purpose: CTR9 is a subunit of the PAF1 complex (PAF1C) that plays a crucial role in transcription regulation by binding CTR9 to RNA polymerase II. It is involved in transcription-coupled histone modification through promoting H3K4 and H3K36 methylation. We describe the clinical and molecular studies in 13 probands, harboring likely pathogenic CTR9 missense variants, collected through GeneMatcher.
View Article and Find Full Text PDFGenome Res
April 2022
Department of Genetic Medicine and Development, University of Geneva Medical Faculty, 1211 Geneva, Switzerland.
The complete, ungapped sequence of the short arms of human acrocentric chromosomes (SAACs) is still unknown almost 20 years after the near completion of the Human Genome Project. Yet these short arms of Chromosomes 13, 14, 15, 21, and 22 contain the ribosomal DNA (rDNA) genes, which are of paramount importance for human biology. The sequences of SAACs show an extensive variation in the copy number of the various repetitive elements, the full extent of which is currently unknown.
View Article and Find Full Text PDFBrief Bioinform
March 2022
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
CoverageMaster (CoM) is a copy number variation (CNV) calling algorithm based on depth-of-coverage maps designed to detect CNVs of any size in exome [whole exome sequencing (WES)] and genome [whole genome sequencing (WGS)] data. The core of the algorithm is the compression of sequencing coverage data in a multiscale Wavelet space and the analysis through an iterative Hidden Markov Model. CoM processes WES and WGS data at nucleotide scale resolution and accurately detects and visualizes full size range CNVs, including single or partial exon deletions and duplications.
View Article and Find Full Text PDFFront Immunol
March 2022
Pediatric Neurology Unit, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics.
View Article and Find Full Text PDFFront Immunol
February 2022
Pediatric Immunology and Vaccinology Unit, General Pediatrics Division, Department for Women, Children, and Teenagers, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Rituximab (RTX) is an anti-CD20 monoclonal antibody that targets B cells-from the immature pre-B-cell stage in the bone marrow to mature circulating B cells-while preserving stem cells and plasma cells. It is used to treat autoimmune diseases, hematological malignancies, or complications after hematopoietic stem cell transplantation (HSCT). Its safety profile is acceptable; however, a subset of patients can develop persistent hypogammaglobulinemia and associated severe complications, especially in pediatric populations.
View Article and Find Full Text PDFNeuromolecular Med
December 2021
The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, 5290002, Ramat-Gan, Israel.
NPJ Genom Med
November 2021
Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland.
Intellectual disability (ID) is a highly heterogeneous disorder with hundreds of associated genes. Despite progress in the identification of the genetic causes of ID following the introduction of high-throughput sequencing, about half of affected individuals still remain without a molecular diagnosis. Consanguineous families with affected individuals provide a unique opportunity to identify novel recessive causative genes.
View Article and Find Full Text PDFGenet Med
October 2021
Division of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC, USA.
Front Immunol
August 2021
The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel.
The risk of severe outcomes following respiratory tract infections is significantly increased in individuals over 60 years, especially in those with chronic medical conditions, i.e., hypertension, diabetes, cardiovascular disease, dementia, chronic respiratory disease, and cancer.
View Article and Find Full Text PDFGenet Med
October 2021
Division of Medical Genetics, Department of Pediatrics, Duke Health, Durham, NC, USA.
Am J Med Genet A
November 2021
University of Geneva Medical School, Geneva, Switzerland.
The past 45 years have witnessed a triumph in the discovery of genes and genetic variation that cause Mendelian disorders due to high impact variants. Important discoveries and organized projects have provided the necessary tools and infrastructure for the identification of gene defects leading to thousands of monogenic phenotypes. This endeavor can be divided in three phases in which different laboratory strategies were employed for the discovery of disease-related genes: (i) the biochemical phase, (ii) the genetic linkage followed by positional cloning phase, and (iii) the sequence identification phase.
View Article and Find Full Text PDFNeuromolecular Med
December 2021
The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, 5290002, Ramat-Gan, Israel.
Genet Med
July 2021
Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
Neuromolecular Med
December 2021
The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, 5290002, Ramat-Gan, Israel.
The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer's disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them.
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