{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:10:14Z","timestamp":1790615414621,"version":"4.1.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p>Background: Hereditary muscle disorders are clinically and genetically heterogeneous. Limited information is available on their genetic makeup and their prevalence in India. Objective: To study the genetic basis of prevalent hereditary myopathies. Material and methods: This is a retrospective study conducted at a tertiary care center. The study was approved by the institutional ethics board. The point of the collection was the genetic database. The genetic data of myopathy patients for the period of two and half years (2019 to mid-2021) was evaluated. Those with genetic diagnoses of DMD, FSHD, myotonic dystrophies, mitochondriopathies, and acquired myopathies were excluded. The main outcome measures were diagnostic yield and the subtype prevalence with their gene variant spectrum. Results: The definitive diagnostic yield of the study was 39% (cases with two pathogenic variants in the disease-causing gene). The major contributing genes were GNE (15%), DYSF (13%), and CAPN3 (7%). Founder genes were documented in Calpainopathy and GNE myopathy. The uncommon myopathies identified were Laminopathy (0.9%), desminopathy (0.9%), and GMPPB-related myopathy (1.9%). Interestingly, a small number of patients showed pathogenic variants in more than one myopathy gene, the multigenic myopathies. Conclusion: This cohort study gives hospital-based information on the prevalent genotypes of myopathies (GNE, Dysferlinopathy, and calpainopathy), founder mutations, and also newly documents the curious occurrence of multigenicity in a small number of myopathies.<\/jats:p>","DOI":"10.3233\/jnd-220801","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T13:26:03Z","timestamp":1655213163000},"page":"571-580","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Appraisal of Hereditary Muscle Disorders In A Cohort From Mumbai, India"],"prefix":"10.1177","volume":"9","author":[{"given":"Satish Vasant","family":"Khadilkar","sequence":"first","affiliation":[{"name":"Department of Neurology, Bombay Hospital, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiral Amrut","family":"Halani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Bombay Hospital, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashna","family":"Dastur","sequence":"additional","affiliation":[{"name":"Centre for Advanced Molecular Diagnostics in Neuromuscular Disorders (CAMDND), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradnya Satish","family":"Gaitonde","sequence":"additional","affiliation":[{"name":"Centre for Advanced Molecular Diagnostics in Neuromuscular Disorders (CAMDND), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsh","family":"Oza","sequence":"additional","affiliation":[{"name":"Department of Neurology, Bombay Hospital, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri","family":"Hegde","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, United States, PerkinElmer Genomics, Global Laboratory Services"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"11","key":"10.3233\/JND-220801_ref2","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1093\/brain\/awp236","article-title":"Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population","volume":"132","author":"Norwood","year":"2009","journal-title":"Brain"},{"issue":"3","key":"10.3233\/JND-220801_ref3","first-page":"138","article-title":"Epidemiology of muscular dystrophies in the Mediterranean area","volume":"32","author":"Topaloglu","year":"2013","journal-title":"Acta Myologica"},{"issue":"1","key":"10.3233\/JND-220801_ref4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1212\/WNL.0000000000002800","article-title":"The genetic basis of undiagnosed muscular dystrophies and myopathies: results from 504 patients","volume":"87","author":"Savarese","year":"2016","journal-title":"Neurology"},{"issue":"4","key":"10.3233\/JND-220801_ref5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3988\/jcn.2013.9.4.280","article-title":"A case of GNE myopathy presenting a rapid deterioration during pregnancy","volume":"9","author":"Sim","year":"2013","journal-title":"Journal of Clinical Neurology"},{"issue":"4","key":"10.3233\/JND-220801_ref6","doi-asserted-by":"crossref","first-page":"e0175343","DOI":"10.1371\/journal.pone.0175343","article-title":"Mutational spectrum of Chinese LGMDpatients by targeted next-generation sequencing","volume":"12","author":"Yu","year":"2017","journal-title":"PloS One"},{"issue":"4","key":"10.3233\/JND-220801_ref7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1136\/jnnp-2013-307051","article-title":"GNE myopathy: current update and future therapy","volume":"86","author":"Nishino","year":"2015","journal-title":"Journal of Neurology, Neurosurgery & Psychiatry"},{"issue":"s2","key":"10.3233\/JND-220801_ref8","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.3233\/JND-150087","article-title":"GNE Myopathy: Two Clusters with History and Several Founder Mutations","volume":"2","author":"Argov","year":"2015","journal-title":"J Neuromuscul Dis"},{"issue":"8","key":"10.3233\/JND-220801_ref9","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1002\/humu.22583","article-title":"Mutation update for GNE gene variants associated with GNE myopathy","volume":"35","author":"Celeste","year":"2014","journal-title":"Hum Mutat"},{"issue":"1","key":"10.3233\/JND-220801_ref10","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3233\/JND-170270","article-title":"Mutation Spectrum of GNE Myopathy in the Indian Sub-Continent","volume":"5","author":"Bhattacharya","year":"2018","journal-title":"J Neuromuscul Dis"},{"issue":"4","key":"10.3233\/JND-220801_ref11","doi-asserted-by":"publisher","first-page":"371","DOI":"10.4103\/0028-3886.117609","article-title":"GNE myopathy in India","volume":"61","author":"Nalini","year":"2013","journal-title":"Neurol India"},{"key":"10.3233\/JND-220801_ref12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.jns.2017.02.005","article-title":"A report on GNE myopathy: Individuals of Rajasthan ancestry share the Roma gene","volume":"375","author":"Khadilkar","year":"2017","journal-title":"J Neurol Sci"},{"issue":"3","key":"10.3233\/JND-220801_ref13","first-page":"185","article-title":"Diagnosis by protein analysis of dysferlinopathy in two patients mistaken as polymyositis","volume":"30","author":"Angelini","year":"2011","journal-title":"Acta Myol"},{"issue":"9","key":"10.3233\/JND-220801_ref14","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1002\/humu.24036","article-title":"The genetic profile of dysferlinopathy in a cohort of 209 cases: Genotype-phenotype relationship and a hotspot on the inner DysF domain","volume":"41","author":"Izumi","year":"2020","journal-title":"Hum Mutat"},{"issue":"2","key":"10.3233\/JND-220801_ref15","doi-asserted-by":"publisher","first-page":"E345","DOI":"10.1002\/humu.20910","article-title":"Analysis of the DYSF mutational spectrum in a large cohort of patients","volume":"30","author":"Krahn","year":"2009","journal-title":"Hum Mutat"},{"issue":"5","key":"10.3233\/JND-220801_ref16","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.nmd.2011.02.003","article-title":"Novel ancestral Dysferlin splicing mutation which migrated from the Iberian peninsula to South America","volume":"21","author":"Vernengo","year":"2011","journal-title":"Neuromuscul Disord"},{"issue":"5","key":"10.3233\/JND-220801_ref17","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1093\/hmg\/8.5.871","article-title":"Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s)","volume":"8","author":"Weiler","year":"1999","journal-title":"Hum Mol Genet"},{"issue":"11-12","key":"10.3233\/JND-220801_ref18","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.nmd.2007.07.010","article-title":"Dysferlinopathy in the Jews of the Caucasus: a frequent mutation in the dysferlin gene","volume":"17","author":"Leshinsky-Silver","year":"2007","journal-title":"Neuromuscul Disord"},{"issue":"10","key":"10.3233\/JND-220801_ref19","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/s0960-8966(03)00133-0","article-title":"Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF mutations and possible founder effect in the Italian population","volume":"13","author":"Cagliani","year":"2003","journal-title":"Neuromuscul Disord"},{"issue":"Pt 6","key":"10.3233\/JND-220801_ref20","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1093\/brain\/123.6.1229","article-title":"Muscular dystrophy due to dysferlin deficiency in Libyan Jews","volume":"123","author":"Argov","year":"2000","journal-title":"Clinical and genetic features. Brain"},{"issue":"8","key":"10.3233\/JND-220801_ref21","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1001\/archneur.62.8.1256","article-title":"Identification of a novel founder mutation in the DYSF gene causing clinical variability in the Spanish population","volume":"62","author":"Vilchez","year":"2005","journal-title":"Arch Neurol"},{"key":"10.3233\/JND-220801_ref22","doi-asserted-by":"crossref","first-page":"119764","DOI":"10.1016\/j.jns.2021.119764","article-title":"Mutational spectrum of dysferlinopathies in a large Indian cohort","volume":"429","author":"Nashi","year":"2021","journal-title":"Journal of the Neurological Sciences"},{"issue":"12","key":"10.3233\/JND-220801_ref23","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1038\/sj.ejhg.5200888","article-title":"Clinical variability in calpainopathy: what makes the difference?","volume":"10","author":"de Paula","year":"2002","journal-title":"Eur J Hum Genet"},{"issue":"6-7","key":"10.3233\/JND-220801_ref25","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S0960-8966(01)00197-3","article-title":"Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy","volume":"11","author":"Chae","year":"2001","journal-title":"Neuromuscular Disorders"},{"issue":"6","key":"10.3233\/JND-220801_ref26","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1002\/mus.23763","article-title":"Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective","volume":"47","author":"Ankala","year":"2013","journal-title":"Muscle Nerve"},{"issue":"1","key":"10.3233\/JND-220801_ref27","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3233\/JND-200547","article-title":"Mutational Spectrum of CAPN3 with Genotype-Phenotype Correlations in Limb Girdle Muscular Dystrophy Type 2A\/R1 (LGMD2A\/LGMDR1) Patients in India","volume":"8","author":"Pathak","year":"2021","journal-title":"J Neuromuscul Dis"},{"issue":"1","key":"10.3233\/JND-220801_ref29","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4103\/0972-2327.175435","article-title":"Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene","volume":"19","author":"Khadilkar","year":"2016","journal-title":"Ann Indian Acad Neurol"},{"issue":"12","key":"10.3233\/JND-220801_ref30","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1136\/jmg.34.12.973","article-title":"Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations","volume":"34","author":"Fanin","year":"1997","journal-title":"Journal of medical genetics"},{"issue":"2","key":"10.3233\/JND-220801_ref31","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.nmd.2017.11.001","article-title":"Phenotypic stratification and genotype-phenotype correlation in aheterogeneous, international cohort of GNE myopathy patients: Firstreport from the GNE myopathy Disease Monitoring Program, registryportion","volume":"28","author":"Pogoryelova","year":"2018","journal-title":"Neuromuscul Disord"},{"issue":"1","key":"10.3233\/JND-220801_ref32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40246-018-0167-1","article-title":"Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients","volume":"12","author":"Fichna","year":"2018","journal-title":"Human genomics"},{"key":"10.3233\/JND-220801_ref33","first-page":"196","article-title":"Digenic Variants in the TTN and TRAPPC11 Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family","volume":"15","author":"Chen","year":"2021","journal-title":"Frontiers in neuroscience"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-220801","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:50:00Z","timestamp":1777506600000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-220801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,1]]},"references-count":30,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jnd-220801","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,1]]}}}