ArticleAmerican journal of human genetics2021
A form of muscular dystrophy associated with pathogenic variants in JAG2.
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Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% of its field
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- PAX7, a Key for Myogenesis Modulation in Muscular Dystrophies through Multiple Signaling Pathways: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Anti-inflammatory and protective effects of Aloe vera on intestinal function in zebrafish.Journal of molecular histology · 2026Article
- Deficiency of muscular dystrophy-related gene JAG2 causes NOTCH signaling dysfunction in muscle stem cells.The Journal of clinical investigation · 2026Article
- Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Genetic variants in Ecuadorian families: unraveling the complexity of non-syndromic cleft lip and palate a case series.BMC oral health · 2026Article
- The impact of Hnrnpl deficiency on transcriptional patterns of developing muscle cells.FEBS open bio · 2026Article
- Genetic disruption of satellite cell function underlying congenital myopathies.Journal of human genetics · 2025Review
- Muscle-specific increased expression ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Zebrafish as a Model Organism for Research in Rare Genetic Neuromuscular Diseases.International journal of molecular sciences · 2025Review
- NOTCH2 mutation in centronuclear myopathy: Beyond the scope.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Deficiency ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.bioRxiv : the preprint server for biology · 2024Article
- Case Report: Exploring the clinical spectrum of LGMD R27: insights from a case study with homozygous pathogenic variant in theFrontiers in pediatrics · 2024Article
- Article
- The Notch signaling pathway in skeletal muscle health and disease.Muscle & nerve · 2022Review
- The Notch signaling network in muscle stem cells during development, homeostasis, and disease.Skeletal muscle · 2022Review
- Defining and identifying satellite cell-opathies within muscular dystrophies and myopathies.Experimental cell research · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
58 authors at 18 institutions in 9 countries.
Sandra CoppensCenter of Human Genetics, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Alison M BarnardDepartment of Physical Therapy, University of Florida College of Public Health and Health Professions, Gainesville, FL 32610, USA.
Sanna PuuseppDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu 50406, Estonia; Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.
Sander PajusaluDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu 50406, Estonia; Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.
Katrin ÕunapDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu 50406, Estonia; Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.
Dorianmarie Vargas-FrancoDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Christine C BruelsDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Sandra DonkervoortNeuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, NIH, Bethesda, MD 20892, USA.
Lynn PaisBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Katherine R ChaoBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Julia K GoodrichBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Eleina M EnglandBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ben WeisburdBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Vijay S GaneshBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Sanna GudmundssonBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Anne O'Donnell-LuriaBroad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Mait NigulDepartment of Radiology, Tartu University Hospital, Tartu 50406, Estonia.
Pilvi IlvesInstitute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia; Department of Radiology, Tartu University Hospital, Tartu 50406, Estonia.
Payam MohasselNeuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, NIH, Bethesda, MD 20892, USA.
Teepu SiddiqueDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Margherita MiloneDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Stefan NicolauDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Reza MaroofianDepartment of Neuromuscular Disorders, University College London Institute of Neurology, London WC1E 6BT, UK.
Henry HouldenDepartment of Neuromuscular Disorders, University College London Institute of Neurology, London WC1E 6BT, UK.
Michael G HannaDepartment of Neuromuscular Disorders, University College London Institute of Neurology, London WC1E 6BT, UK.
Ros QuinlivanDepartment of Neuromuscular Disorders, University College London Institute of Neurology, London WC1E 6BT, UK.
Mehran Beiraghi ToosiPediatric Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad 9176999311, Iran.
Ehsan Ghayoor KarimianiMolecular and Clinical Sciences Institute, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK; Innovative Medical Research Center, Mashhad Branch, Islamic Azad University, Mashhad 9187147578, Iran.
Sabine CostagliolaInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Nicolas DeconinckCentre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium.
Hazim KadhimNeuropathology Unit, Department of Anatomic Pathology and Reference Center for Neuromuscular Pathology, Brugmann University Hospital-Children's Hospital, Université Libre de Bruxelles, 1020 Brussels, Belgium.
Erica MackeCenter for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Brendan C LanpherCenter for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Eric W KleeCenter for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Anna ŁusakowskaDepartment of Neurology, Medical University of Warsaw, 02-091 Warsaw, Poland.
Anna Kostera-PruszczykDepartment of Neurology, Medical University of Warsaw, 02-091 Warsaw, Poland.
Andreas HahnDepartment of Child Neurology, Justus-Liebig-University Giessen, 35390 Giessen, Germany.
Bertold SchrankDepartment of Neurology, DKD HELIOS Klinik Wiesbaden, 65191 Wiesbaden, Germany.
Ichizo NishinoDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan.
Masashi OgasawaraDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan.
Rasha El SherifMyo-Care Neuromuscular Center, Myo-Care National Foundation, Cairo 11865, Egypt.
Tanya StojkovicAPHP, Nord-Est/Ile-de-France Neuromuscular Reference Center, Myology Institute, Pitié-Salpêtrière Hospital, 75013 Paris, France; Sorbonne Université, INSERM, Center of Research in Myology, UMRS974, 75651 Paris Cedex 13, France.
Isabelle NelsonSorbonne Université, INSERM, Center of Research in Myology, UMRS974, 75651 Paris Cedex 13, France.
Gisèle BonneSorbonne Université, INSERM, Center of Research in Myology, UMRS974, 75651 Paris Cedex 13, France.
Enzo CohenSorbonne Université, INSERM, Center of Research in Myology, UMRS974, 75651 Paris Cedex 13, France.
Anne Boland-AugéUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057 Evry, France.
Jean-François DeleuzeUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057 Evry, France.
Yao MengDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Ana TöpfJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 3BZ, UK.
Catheline VilainCenter of Human Genetics, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Christina A PacakDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA; Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Marie L Rivera-ZengotitaDepartment of Pathology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Carsten G BönnemannNeuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, NINDS, NIH, Bethesda, MD 20892, USA.
Volker StraubJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 3BZ, UK.
Penny A HandfordDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Isabelle DraperMolecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Glenn A WalterDepartment of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Peter B KangDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA; Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Institute for Translational Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Electronic address: pkang@umn.edu.
Broad Institute · USUniversity of Florida · USMayo Clinic · USTartu University Hospital · EEUniversité Libre de Bruxelles · BEInserm · FRUniversity College London · GBNational Institutes of Health · USCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRMedical University of Warsaw · PLNational Center of Neurology and Psychiatry · JPNewcastle University · GBUniversity of Oxford · GBJustus-Liebig-Universität Gießen · DEMashhad University of Medical Sciences · IRNorthwestern University · USSt George's, University of London · GBTufts Medical Center · US
Funding
Advanced 3T for Structural and Functional Imaging at University of FloridaS10OD021726 · OD · UNIVERSITY OF FLORIDA · PI LONG, JOANNA R · 2017 to 2017
$2.0MMedical Research Council MR/R009317/1NIH HHS S10 OD021726
Abstract
JAG2 encodes the Notch ligand Jagged2. The conserved Notch signaling pathway contributes to the development and homeostasis of multiple tissues, including skeletal muscle. We studied an international cohort of 23 individuals with genetically unsolved muscular dystrophy from 13 unrelated families. Whole-exome sequencing identified rare homozygous or compound heterozygous JAG2 variants in all 13 families. The identified bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy. Transcriptome analysis of muscle tissue from two participants suggested misregulation of genes involved in myogenesis, including PAX7. In complementary studies, Jag2 downregulation in murine myoblasts led to downregulation of multiple components of the Notch pathway, including Megf10. Investigations in Drosophila suggested an interaction between Serrate and Drpr, the fly orthologs of JAG1/JAG2 and MEGF10, respectively. In silico analysis predicted that many Jagged2 missense variants are associated with structural changes and protein misfolding. In summary, we describe a muscular dystrophy associated with pathogenic variants in JAG2 and evidence suggests a disease mechanism related to Notch pathway dysfunction.
Indexed as
AdolescentAdultAmino Acid SequenceAnimalsCell LineChildChild, PreschoolDrosophila melanogasterDrosophila ProteinsExome SequencingFemaleGlucosyltransferasesHaplotypesHumansJagged-1 ProteinJagged-2 ProteinDrosophila Proteinsdrpr protein, DrosophilaGlucosyltransferasesJAG2 protein, humanJagged-1 ProteinJagged-2 ProteinMEGF10, humanMembrane ProteinsPOGLUT1 protein, humanReceptors, NotchSer protein, DrosophilaJAG2, Jagged2, Serrate, Notch signaling pathway, muscular dystrophy, muscle MRI, POGLUT1, MEGF10, exome sequencing, satellite cell
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