Titre
Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Mohan, S.
Auteure/Auteur
McNulty, S.
Auteure/Auteur
Thaxton, C.
Auteure/Auteur
Elnagheeb, M.
Auteure/Auteur
Owens, E.
Auteure/Auteur
Flowers, M.
Auteure/Auteur
Nunnery, T.
Auteure/Auteur
Self, A.
Auteure/Auteur
Palus, B.
Auteure/Auteur
Gorokhova, S.
Auteure/Auteur
Kennedy, A.
Auteure/Auteur
Niu, Z.
Auteure/Auteur
Johari, M.
Auteure/Auteur
Maiga, A.B.
Auteure/Auteur
Macalalad, K.
Auteure/Auteur
Clause, A.R.
Auteure/Auteur
Beckmann, J.S.
Auteure/Auteur
Bronicki, L.
Auteure/Auteur
Cooper, S.T.
Auteure/Auteur
Ganesh, V.S.
Auteure/Auteur
Kang, P.B.
Auteure/Auteur
Kesari, A.
Auteure/Auteur
Lek, M.
Auteure/Auteur
Levy, J.
Auteure/Auteur
Rufibach, L.
Auteure/Auteur
Savarese, M.
Auteure/Auteur
Spencer, M.J.
Auteure/Auteur
Straub, V.
Auteure/Auteur
Tasca, G.
Auteure/Auteur
Weihl, C.C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2328-9503
Statut éditorial
Publié
Date de publication
2024-09
Volume
11
Numéro
9
Première page
2268
Dernière page/numéro d’article
2276
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.
The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD.
The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD.
The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.
The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD.
The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD.
The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.
PID Serval
serval:BIB_8E8769949B9B
PMID
Open Access
Oui
Date de création
2024-09-10T13:02:39.526Z
Date de création dans IRIS
2025-05-20T23:07:55Z
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Nom
39215466_BIB_8E8769949B9B.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
1.1 MB
Format
Adobe PDF
PID Serval
serval:BIB_8E8769949B9B.P001
URN
urn:nbn:ch:serval-BIB_8E8769949B9B0
Somme de contrôle
(MD5):e0d4141f1b528f48d20e245a1053b268