{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:16:37Z","timestamp":1760238997680,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Graduate University of Science and Technology, Vietnam Academic of Science and Technology","award":["GUST.STS.\u0110T2017-SH02"],"award-info":[{"award-number":["GUST.STS.\u0110T2017-SH02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Muscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for obtaining a precise diagnosis without the need for immunohistochemistry. WES was performed in the two siblings and their parents, followed by prioritization of variants and validation by Sanger sequencing. Very rare variants with moderate to high predicted impact in genes associated with neuromuscular disorders were selected. We identified two pathogenic missense variants, c.778C&gt;T (p.H260Y) and c.2987G&gt;A (p.C996Y), in the LAMA2 gene (NM_000426.3), in the homozygous state in two siblings, and in the heterozygous state in their unaffected parents, which were confirmed by Sanger sequencing. Variant c.2987G&gt;A has not been reported previously. These variants may lead to a change in the structure and function of laminin-\u03b12, a member of the family of laminin-211, which is an extracellular matrix protein that functions to stabilize the basement membrane of muscle fibers during contractions. Overall, WES enabled an accurate diagnosis of both patients with LAMA2-related muscular dystrophy and expanded the spectrum of missense variants in LAMA2.<\/jats:p>","DOI":"10.3390\/diagnostics10100741","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T08:33:03Z","timestamp":1600936383000},"page":"741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7305-6505","authenticated-orcid":false,"given":"Ngoc-Lan","family":"Nguyen","sequence":"first","affiliation":[{"name":"Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Vietnam"},{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can Thi Bich","family":"Ngoc","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases and Newborn Screening, Department of Endocrinology, Metabolism and Genetics, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh str., Dong Da, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi Dung","family":"Vu","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases and Newborn Screening, Department of Endocrinology, Metabolism and Genetics, Vietnam National Children\u2019s Hospital, 18\/879 La Thanh str., Dong Da, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi Thu Huong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6284-5813","authenticated-orcid":false,"given":"Huy Hoang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Vietnam"},{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s10038-006-0056-7","article-title":"The genetic and molecular basis of muscular dystrophy: Roles of cell\u2013matrix linkage in the pathogenesis","volume":"51","author":"Kanagawa","year":"2006","journal-title":"J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/S0140-6736(19)32910-1","article-title":"Muscular dystrophies","volume":"394","author":"Mercuri","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S0140-6736(12)61897-2","article-title":"Muscular dystrophies","volume":"381","author":"Mercuri","year":"2013","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000088674","article-title":"Epidemiological study of muscular disorders in Assiut, Egypt","volume":"25","author":"Khedr","year":"2005","journal-title":"Neuroepidemiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13052-016-0289-9","article-title":"Congenital muscular dystrophy: From muscle to brain","volume":"42","author":"Falsaperla","year":"2016","journal-title":"Ital. J. Paediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.spen.2011.10.010","article-title":"Congenital muscular dystrophies: A brief review","volume":"18","author":"Bertini","year":"2011","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/ana.24687","article-title":"Diagnosis and etiology of congenital muscular dystrophy: We are halfway there","volume":"80","author":"Lek","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.nmd.2019.10.010","article-title":"The 2020 version of the gene table of neuromuscular disorders (nuclear genome)","volume":"29","author":"Benarroch","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1212\/WNL.0000000000001303","article-title":"Prevalence of congenital muscular dystrophy in Italy","volume":"84","author":"Graziano","year":"2015","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/cge.13560","article-title":"Congenital muscular dystrophies in China","volume":"96","author":"Ge","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.nmd.2010.02.001","article-title":"Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations","volume":"20","author":"Geranmayeh","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/sj.ejhg.5200743","article-title":"Merosin-deficient congenital muscular dystrophy, autosomal recessive (MDC1A, MIM#156225, LAMA2 gene coding for \u03b12 chain of laminin)","volume":"10","author":"Allamand","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.nmd.2017.06.008","article-title":"Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period","volume":"27","author":"Sframeli","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/mus.24588","article-title":"LAMA2-related myopathy: Frequency among congenital and limb-girdle muscular dystrophies","volume":"52","author":"Born","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.nmd.2020.03.009","article-title":"Clinical and genomic characteristics of LAMA2 related congenital muscular dystrophy in a patients\u2019 cohort from Qatar. A population specific founder variant","volume":"30","author":"Elsaid","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1083\/jcb.200611152","article-title":"Linker molecules between laminins and dystroglycan ameliorate laminin-\u03b12\u2013deficient muscular dystrophy at all disease stages","volume":"176","author":"Meinen","year":"2007","journal-title":"J. Cell. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gawlik, K.I., and Durbeej, M. (2011). Skeletal muscle laminin and MDC1A: Pathogenesis and treatment strategies. Skelet. Muscle, 1.","DOI":"10.1186\/2044-5040-1-9"},{"key":"ref_18","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Stephens, K., and Amemiya, A. (2012). LAMA2-related muscular dystrophy. GeneReviews\u00ae, University of Washington."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.3892\/etm.2013.1271","article-title":"Merosin-deficient congenital muscular dystrophy type 1A: A case report","volume":"6","author":"He","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fgene.2018.00043","article-title":"Identification of two novel LAMA2 mutations in a Chinese patient with congenital muscular dystrophy","volume":"9","author":"Zhou","year":"2018","journal-title":"Front. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.nmd.2019.04.001","article-title":"Exome sequencing detects compound heterozygous nonsense LAMA2 mutations in two siblings with atypical phenotype and nearly normal brain MRI","volume":"29","author":"Saredi","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1002\/1097-4598(200010)23:10<1456::AID-MUS2>3.0.CO;2-T","article-title":"Molecular basis of muscular dystrophies","volume":"23","author":"Cohn","year":"2000","journal-title":"Muscle Nerve"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sakuma, K. (2019). Clinical and molecular diagnosis in muscular dystrophies. Muscular Dystrophies, IntechOpen.","DOI":"10.5772\/intechopen.73974"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.nmd.2013.12.011","article-title":"Diagnostic approach to the congenital muscular dystrophies","volume":"24","author":"Wang","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/humu.23599","article-title":"LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-\u03b12 variome and its related phenotypes","volume":"39","author":"Oliveira","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s13353-016-0365-2","article-title":"Limb-girdle muscular dystrophy with severe heart failure overlapping with lipodystrophy in a patient with LMNA mutation p.Ser334del","volume":"58","author":"Niezgoda","year":"2017","journal-title":"J. Appl. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1136\/jmg.2005.031963","article-title":"POMT2 mutations cause \u03b1-dystroglycan hypoglycosylation and Walker-Warburg syndrome","volume":"42","author":"Janssen","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.nmd.2006.03.016","article-title":"POMT2 mutation in a patient with \u2018MEB-like\u2019 phenotype","volume":"16","author":"Mercuri","year":"2006","journal-title":"Neuromuscul. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.bbrc.2007.09.066","article-title":"POMT2 gene mutation in limb-girdle muscular dystrophy with inflammatory changes","volume":"363","author":"Biancheri","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/mus.26782","article-title":"Emery-Dreifuss muscular dystrophy","volume":"61","author":"Heller","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7874","DOI":"10.1002\/jcp.27907","article-title":"Prevalence, pathological mechanisms, and genetic basis of limb-girdle muscular dystrophies: A review","volume":"234","author":"Taghizadeh","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dardas, Z., Swedan, S., Al-Sheikh Qassem, A., and Azab, B. (2020). The impact of exome sequencing on the diagnostic yield of muscular dystrophies in consanguineous families. Eur. J. Med. Genet., 63.","DOI":"10.1016\/j.ejmg.2020.103845"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/WCO.0000000000000374","article-title":"Next generation sequencing in neuromuscular diseases","volume":"29","author":"Efthymiou","year":"2016","journal-title":"Curr. Opin. Neurol."},{"key":"ref_34","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. Genom."},{"key":"ref_35","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."},{"key":"ref_36","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."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.nmd.2018.09.006","article-title":"The 2019 version of the gene table of neuromuscular disorders (nuclear genome)","volume":"28","author":"Bonne","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cca.2020.05.010","article-title":"A novel frameshift PHKA2 mutation in a family with glycogen storage disease type IXa: A first report in Vietnam and review of literature","volume":"508","author":"Nguyen","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_40","first-page":"46","article-title":"A novel de novo variant of LAMA2 contributes to merosin deficient congenital muscular dystrophy type 1A: Case report","volume":"12","author":"Tran","year":"2020","journal-title":"Biomed. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3233\/JND-150093","article-title":"Laminin \u03b12 deficiency-related muscular dystrophy mimicking Emery-Dreifuss and collagen VI related diseases","volume":"2","author":"Nelson","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/cge.12366","article-title":"Genotype\/phenotype analysis in Chinese laminin-\u03b12 deficient congenital muscular dystrophy patients","volume":"87","author":"Xiong","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fnmol.2019.00305","article-title":"Linker protein repair of LAMA2 dystrophic neuromuscular basement membranes","volume":"12","author":"Yurchenco","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1212\/WNL.0000000000003958","article-title":"Child Neurology: LAMA2 muscular dystrophy without contractures","volume":"88","author":"Dean","year":"2017","journal-title":"Neurology"},{"key":"ref_45","first-page":"1177","article-title":"Substitution of a conserved cysteine-996 in a cysteine-rich motif of the laminin alpha2-chain in congenital muscular dystrophy with partial deficiency of the protein","volume":"58","author":"Nissinen","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"877","DOI":"10.2169\/internalmedicine.9588-17","article-title":"A homozygous LAMA2 mutation of c.818G>A caused partial merosin deficiency in a Japanese patient","volume":"57","author":"Kubota","year":"2018","journal-title":"Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"408","DOI":"10.29252\/.22.6.408","article-title":"Novel LAMA2 gene mutations associated with merosin-deficient congenital muscular dystrophy","volume":"22","author":"Yassaee","year":"2018","journal-title":"Iran Biomed. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100","DOI":"10.5414\/NP301137","article-title":"Missense mutations in LAMA2 causing a new phenotype of mild cognitive impairment, proximal myopathy, seizure, and severe leukoencephalopathy: A case report and protein analysis","volume":"38","author":"Ding","year":"2019","journal-title":"Clin. Neuropathol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/10\/741\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:13:13Z","timestamp":1760177593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/10\/741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["diagnostics10100741"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10100741","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2020,9,24]]}}}