{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:10:03Z","timestamp":1777857003171,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2021,3,2]]},"abstract":"<jats:p>Background: A Dutch cohort of 105 carefully selected limb girdle muscular dystrophy (LGMD) patients from 68 families has been subject to genetic testing over the last 20 years. After subsequent targeted gene analysis around two thirds (45\/68) of the families had received a genetic diagnosis in 2013. Objective: To describe the results of further genetic testing in the remaining undiagnosed limb girdle muscular dystrophy families in this cohort. Methods: In the families of the cohort for whom no genetic diagnosis was established (n\u200a=\u200a23) further testing using Sanger sequencing, next generation sequencing with gene panel analysis or whole-exome sequencing was performed. In one case DNA analysis for facioscapulohumeral dystrophy type 1 was carried out. Results: In eight families no additional genetic tests could be performed. In 12 of the remaining 15 families in which additional testing could be performed a genetic diagnosis was established: two LGMDR1 calpain3-related families with CAPN3 mutations, one LGMDR2 dysferlin-related family with DYSF mutations, three sarcoglycanopathy families (LGMDR3-5 \u03b1-, \u03b2- and \u03b3-sarcoglycan-related) with SGCA\/SGCB\/SGCG mutations, one LGMDR8 TRIM 32-related family with TRIM32 mutations, two LGMDR19 GMPPB-related families with GMPPB mutations, one family with MICU1-related myopathy, one family with FLNC-related myopathy and one family with facioscapulohumeral dystrophy type 1. At this moment a genetic diagnosis has been made in 57 of the 60 families of which DNA was available (95%). Conclusion: A genetic diagnosis is obtained in 95% of the families of the original Dutch LGMD cohort of which DNA was available.<\/jats:p>","DOI":"10.3233\/jnd-200585","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T11:05:54Z","timestamp":1609239954000},"page":"261-272","source":"Crossref","is-referenced-by-count":5,"title":["Elucidation of the Genetic Cause in Dutch Limb Girdle Muscular Dystrophy Families: A 27-Year\u2019s Journey"],"prefix":"10.1177","volume":"8","author":[{"given":"L.","family":"ten Dam","sequence":"first","affiliation":[{"name":"Department of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"de Visser","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ieke B.","family":"Ginjaar","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermine A.","family":"van Duyvenvoorde","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana","family":"van Koningsbruggen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneke J.","family":"van der Kooi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"issue":"Pt 5","key":"10.3233\/JND-200585_ref1","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1093\/brain\/119.5.1471","article-title":"The clinical spectrum of limb girdle muscular dystrophy. A survey in The Netherlands","volume":"119","author":"van der Kooi","year":"1996","journal-title":"Brain"},{"issue":"24","key":"10.3233\/JND-200585_ref2","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1212\/01.wnl.0000264853.40735.3b","article-title":"Limb-girdle muscular dystrophy in the Netherlands: Gene defect identified in half the families","volume":"68","author":"van der Kooi","year":"2007","journal-title":"Neurology"},{"key":"10.3233\/JND-200585_ref3","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.nmd.2013.03.012","article-title":"ANO5 mutations in the Dutch limb girdle muscular dystrophy population","volume":"23","author":"van der Kooi","year":"2013","journal-title":"Neuromuscul Disord"},{"issue":"8","key":"10.3233\/JND-200585_ref4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.nmd.2018.05.007","article-title":"229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017","volume":"28","author":"Straub","year":"2018","journal-title":"Neuromuscul Disord"},{"issue":"16","key":"10.3233\/JND-200585_ref5","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1212\/WNL.0b013e3181a1885e","article-title":"Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes","volume":"72","author":"Fanin","year":"2009","journal-title":"Neurology"},{"issue":"11","key":"10.3233\/JND-200585_ref6","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.nmd.2012.05.001","article-title":"Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients","volume":"22","author":"Magri","year":"2012","journal-title":"Neuromuscul Disord"},{"issue":"5","key":"10.3233\/JND-200585_ref7","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/ana.20824","article-title":"High prevalence and phenotype-genotype correlations of limb-girdle muscular dystrophy type 2I in Denmark","volume":"59","author":"Sveen","year":"2009","journal-title":"Ann Neurol"},{"key":"10.3233\/JND-200585_ref8","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1007\/s00415-013-6934-y","article-title":"Anoctamin 5 muscular dystrophy in Denmark: Prevalence genotypes, phenotypes, cardiac findings and muscle protein expression","volume":"260","author":"Witting","year":"2013","journal-title":"J Neurol"},{"issue":"4","key":"10.3233\/JND-200585_ref11","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/emm.2001.41","article-title":"Point mutation and polymorphism in Duchenne\/Becker muscular dystrophy (D\/BMD) patients","volume":"33","author":"Chaturvedi","year":"2001","journal-title":"Exp Mol Med"},{"key":"10.3233\/JND-200585_ref12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.gde.2015.08.007","article-title":"Genetic and epigenetic contributors to FSHD","volume":"33","author":"Daxinger","year":"2015","journal-title":"Curr Opin Genet Dev"},{"issue":"4","key":"10.3233\/JND-200585_ref13","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s13311-018-00674-4","article-title":"Diagnosis and Treatment of Mitochondrial Myopathies","volume":"15","author":"Ahmed","year":"2018","journal-title":"Neurotherapeutics"},{"issue":"10","key":"10.3233\/JND-200585_ref14","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1080\/14737159.2018.1523723","article-title":"The clinical implementation of copy number detection in the age of next-generation sequencing","volume":"18","author":"Hehir-Kwa","year":"2018","journal-title":"Expert Rev Mol Diagn"},{"key":"10.3233\/JND-200585_ref15","first-page":"200","article-title":"Accuracy of short tandem repeats genotyping tools in whole exome sequencing data","volume":"9","author":"Halman","year":"2020","journal-title":"FRes"},{"issue":"3","key":"10.3233\/JND-200585_ref16","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/jlb\/lsx038","article-title":"The known unknown: The challenges of genetic variants of uncertain significance in clinical practice","volume":"4","author":"Hoffman-Andrews","year":"2017","journal-title":"J Law Biosci"},{"issue":"12","key":"10.3233\/JND-200585_ref17","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1093\/hmg\/5.12.1997","article-title":"Evidence for subtelomeric exchange of 3.3 kb tandemly repeated units between chromosomes 4q35 and 10q Implications for genetic counselling and etiology of FSHD1","volume":"5","author":"van Deutekom","year":"1996","journal-title":"Hum Mol Genet"},{"issue":"2","key":"10.3233\/JND-200585_ref18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/cge.13544","article-title":"Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients","volume":"96","author":"ten Dam","year":"2019","journal-title":"Clin Genet"},{"issue":"7","key":"10.3233\/JND-200585_ref19","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s004150070151","article-title":"Sarcoglycanopathies in Dutch patients with autosomal recessive limb girdle muscular dystrophy","volume":"247","author":"Ginjaar","year":"2000","journal-title":"J Neurol"},{"issue":"4","key":"10.3233\/JND-200585_ref20","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S0002-9440(10)65354-0","article-title":"Multiplex Western blotting system for the analysis of muscular dystrophy proteins","volume":"154","author":"Anderson","year":"1999","journal-title":"Am J Pathol"},{"issue":"1","key":"10.3233\/JND-200585_ref21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1136\/hrt.79.1.73","article-title":"The heart in limb girdle muscular dystrophy","volume":"79","author":"van der Kooi","year":"1998","journal-title":"Heart"},{"issue":"9","key":"10.3233\/JND-200585_ref22","doi-asserted-by":"crossref","first-page":"E1658","DOI":"10.1002\/humu.21320","article-title":"Transcriptional and translational effects of intronic CAPN3 gene mutations","volume":"31","author":"Nascimbeni","year":"2010","journal-title":"Hum Mutat"},{"issue":"9","key":"10.3233\/JND-200585_ref23","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1136\/jmg.2004.028738","article-title":"Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes","volume":"42","author":"Piluso","year":"2005","journal-title":"J Med Genet"},{"issue":"2","key":"10.3233\/JND-200585_ref24","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/humu.20633","article-title":"Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H","volume":"29","author":"Saccone","year":"2008","journal-title":"Hum Mutat"},{"issue":"3","key":"10.3233\/JND-200585_ref25","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1086\/339083","article-title":"Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene","volume":"70","author":"Frosk","year":"2002","journal-title":"Am J Hum Genet"},{"issue":"6","key":"10.3233\/JND-200585_ref26","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1212\/NXG.0000000000000112","article-title":"Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T)","volume":"2","author":"Oestergaard","year":"2016","journal-title":"Neurol Genet"},{"issue":"1","key":"10.3233\/JND-200585_ref27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ajhg.2013.05.009","article-title":"Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan","volume":"93","author":"Carss","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"6","key":"10.3233\/JND-200585_ref28","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.nmd.2010.03.009","article-title":"A novel heterozygous deletion-insertion mutation -del\/GTTTGT ins) in exon 18 of the filamin C gene causes filaminopathy in a large Chinese family","volume":"20","author":"Luan","year":"2010","journal-title":"Neuromuscul Disord"},{"issue":"1","key":"10.3233\/JND-200585_ref29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.nmd.2015.10.003","article-title":"Targeted next-generation sequencing assay for detection of mutations in primary myopathies","volume":"26","author":"Evila","year":"2016","journal-title":"Neuromuscul Disord"},{"issue":"Pt 9","key":"10.3233\/JND-200585_ref30","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1093\/brain\/aws200","article-title":"Pathophysiology of protein aggregation and extended phenotyping in filaminopathy","volume":"135","author":"Kley","year":"2012","journal-title":"Brain"},{"issue":"12","key":"10.3233\/JND-200585_ref31","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.nmd.2008.08.003","article-title":"Sarcoglycanopathies: Can muscle immunoanalysis predict the genotype?","volume":"18","author":"Klinge","year":"2008","journal-title":"Neuromuscul Disord"},{"issue":"1","key":"10.3233\/JND-200585_ref32","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13023-018-0863-x","article-title":"Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: An Italian cross-sectional study","volume":"13","author":"Astrea","year":"2018","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"10.3233\/JND-200585_ref33","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.nmd.2017.03.004","article-title":"Novel mutations in the C-terminal region of GMPPB causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome","volume":"27","author":"Luo","year":"2017","journal-title":"Neuromuscul Disord"},{"issue":"10","key":"10.3233\/JND-200585_ref34","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1001\/archneur.60.10.1421","article-title":"Atypical phenotypes in patients with facioscapulohumeral muscular dystrophy 4q35 deletion","volume":"60","author":"Krasnianski","year":"2003","journal-title":"Arch Neurol"},{"issue":"6","key":"10.3233\/JND-200585_ref35","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/mus.26474","article-title":"Phenotype may predict the clinical course of facioscapolohumeral muscular dystrophy","volume":"59","author":"Ricci","year":"2019","journal-title":"Muscle Nerve"},{"issue":"2","key":"10.3233\/JND-200585_ref36","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/ene.13509","article-title":"Clinical and genetic features of patients with facial-sparing facioscapulohumeral muscular dystrophy","volume":"25","author":"He","year":"2018","journal-title":"Eur J Neurol"},{"issue":"13","key":"10.3233\/JND-200585_ref37","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1212\/WNL.0000000000000828","article-title":"Severe paraspinal muscle involvement in facioscapulohumeral muscular dystrophy","volume":"83","author":"Dahlqvist","year":"2014","journal-title":"Neurology"},{"issue":"4","key":"10.3233\/JND-200585_ref38","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/mus.24569","article-title":"Whole-body magnetic resonance imaging evaluation of facioscapulohumeral muscular dystrophy","volume":"52","author":"Leung","year":"2015","journal-title":"Muscle Nerve"},{"issue":"Pt 12","key":"10.3233\/JND-200585_ref39","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1093\/brain\/awm271","article-title":"Clinical and morphological phenotype of the filamin myopathy: A study of 31 German patients","volume":"130","author":"Kley","year":"2007","journal-title":"Brain"},{"issue":"1","key":"10.3233\/JND-200585_ref40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.nmd.2016.09.017","article-title":"Widening the spectrum of filamin-C myopathy: Predominantly proximal myopathy due to the A193T mutation in the actin-binding domain of FLNC","volume":"27","author":"van den Bogaart","year":"2017","journal-title":"Neuromuscul Disord"},{"issue":"4 Pt 2","key":"10.3233\/JND-200585_ref41","doi-asserted-by":"crossref","first-page":"e249","DOI":"10.1016\/j.lpm.2010.11.023","article-title":"Myositis or dystrophy? Traps and pitfalls","volume":"40","author":"Benveniste","year":"2011","journal-title":"Presse Med"},{"issue":"5","key":"10.3233\/JND-200585_ref42","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/ahg.12319","article-title":"Impact of next-generation sequencing panels in the evaluation of limb-girdle muscular dystrophies","volume":"83","author":"Ozyilmaz","year":"2019","journal-title":"Ann Hum Genet"},{"issue":"4","key":"10.3233\/JND-200585_ref43","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s00415-016-8036-0","article-title":"Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy","volume":"263","author":"Kuhn","year":"2016","journal-title":"J Neurol"},{"issue":"12","key":"10.3233\/JND-200585_ref44","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1001\/jamaneurol.2015.2274","article-title":"Use of Whole-Exome Sequencing for Diagnosis of Limb-Girdle Muscular Dystrophy: Outcomes and Lessons Learned","volume":"72","author":"Ghaoui","year":"2015","journal-title":"JAMA Neurol"},{"issue":"1","key":"10.3233\/JND-200585_ref45","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s13023-017-0699-9","article-title":"Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy","volume":"12","author":"Harris","year":"2017","journal-title":"Orphanet J Rare Dis"},{"issue":"2","key":"10.3233\/JND-200585_ref46","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/jhg.2016.116","article-title":"The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States","volume":"62","author":"Reddy","year":"2017","journal-title":"J Hum Genet"},{"issue":"1","key":"10.3233\/JND-200585_ref47","doi-asserted-by":"crossref","first-page":"34","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":"Hum Genomics"},{"key":"10.3233\/JND-200585_ref48","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0840-3"},{"issue":"2","key":"10.3233\/JND-200585_ref49","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3233\/JND-180376","article-title":"Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service","volume":"6","author":"Westra","year":"2019","journal-title":"J Neuromuscul Dis"},{"issue":"3","key":"10.3233\/JND-200585_ref50","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ajhg.2019.01.012","article-title":"Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease","volume":"104","author":"Gonorazky","year":"2019","journal-title":"Am J Hum Genet"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-200585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:49:36Z","timestamp":1777506576000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-200585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,2]]},"references-count":48,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jnd-200585","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,2]]}}}