{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:11:20Z","timestamp":1753891880162,"version":"3.41.2"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T00:00:00Z","timestamp":1687132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171848"],"award-info":[{"award-number":["82171848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901382"],"award-info":[{"award-number":["81901382"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Mutations of <jats:italic>LAMA2<\/jats:italic> gene are associated with congenital muscular dystrophy (CMD). The <jats:italic>LAMA2<\/jats:italic>-related CMD mainly consists of two diseases, merosin deficient congenital muscular dystrophies type 1A (MDC1A) and limb girdle muscular dystrophy 23 (LGMD23). LGMD23 is characterized by slowly progressive proximal muscle weakness, which primarily affects the lower limbs and results in gait difficulties. Additional clinical features include increased serum creatine kinase, abnormal electromyography with or without white matter abnormalities on brain imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data were collected from a Chinese Han family. Whole-exome sequencing, Sanger sequencing, RT-PCR and TA clone sequencing were performed on the family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compound heterozygous mutations of <jats:italic>LAMA2<\/jats:italic>: c.1693C\u2009&amp;gt;\u2009T (<jats:italic>p<\/jats:italic>. Q565*) (maternally inherited) and c.9212-6T\u2009&amp;gt;\u2009G (paternally inherited) were identified and confirmed in the proband. The mutation c.1693C\u2009&amp;gt;\u2009T (<jats:italic>p<\/jats:italic>. Q565*) was classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. By performing RT-PCR and TA clone sequencing, an insertion of 40-bp intronic sequence (intron 64) was found in the transcripts of the proband and her father, which resulted in a frameshift and premature truncation codon of the <jats:italic>LAMA2<\/jats:italic>. In particular, the variant truncated the LamG domain of the LAMA2. Therefore, the c.9212-6T&amp;gt;G was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings described two novel mutations in a girl with LGMDR23, which contributes to the genetic counseling of the family and expands the clinical and molecular spectrums of the rare disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1191068","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T10:14:03Z","timestamp":1687169643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Limb girdle muscular dystrophy 23 caused by compound heterozygous mutations of LAMA2 gene"],"prefix":"10.3389","volume":"11","author":[{"given":"Yuqing","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeqing","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minyue","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.biocel.2007.07.015","article-title":"Bridging structure with function: structural, regulatory, and developmental role of laminins","volume":"40","author":"Tzu","year":"2008","journal-title":"Int J Biochem Cell Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1172\/JCI119716","article-title":"Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy","volume":"100","author":"Vachon","year":"1997","journal-title":"J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","first-page":"21437","DOI":"10.1074\/jbc.M702963200","article-title":"Role of laminin terminal globular domains in basement membrane assembly","volume":"282","author":"McKee","year":"2007","journal-title":"J Biol Chem"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1096\/fasebj.4.6.2180767","article-title":"Molecular architecture of basement membranes","volume":"4","author":"Yurchenco","year":"1990","journal-title":"FASEB J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1083\/jcb.117.5.1119","article-title":"Laminin forms an independent network in basement membranes","volume":"117","author":"Yurchenco","year":"1992","journal-title":"J Cell Biol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1212\/WNL.0000000000001303","article-title":"Prevalence of congenital muscular dystrophy in Italy: a population study","volume":"84","author":"Graziano","year":"2015","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.nmd.2018.05.007","article-title":"229th ENMC international workshop: limb girdle muscular dystrophies\u2014nomenclature and reformed classification Naarden, the Netherlands, 17\u201319 March 2017","volume":"28","author":"Straub","year":"2018","journal-title":"Neuromuscul Disord"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/S0140-6736(05)63023-1","article-title":"A benign allelic form of laminin alpha 2 chain deficient muscular dystrophy","volume":"349","author":"Hayashi","year":"1997","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/S0960-8966(98)00065-0","article-title":"Laminin alpha 2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy","volume":"8","author":"Naom","year":"1998","journal-title":"Neuromuscul Disord"},{"key":"B12","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1002\/mus.22196","article-title":"Clinical and pathological heterogeneity in late-onset partial merosin deficiency","volume":"44","author":"Rajakulendran","year":"2011","journal-title":"Muscle Nerve"},{"key":"B13","doi-asserted-by":"publisher","first-page":"978688","DOI":"10.3389\/fgene.2022.978688","article-title":"Case report: novel splicing mutations in RFX5 causing MHC class II deficiency","volume":"13","author":"Chen","year":"2022","journal-title":"Front Genet"},{"key":"B14","first-page":"351","article-title":"Congenital muscular dystrophy with merosin deficiency","volume":"317","author":"Tom\u00e9","year":"1994","journal-title":"C R Acad Sci III"},{"key":"B15","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/ng1095-216","article-title":"Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy","volume":"11","author":"Helbling-Leclerc","year":"1995","journal-title":"Nat Genet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/0960-8966(95)90011-X","article-title":"Proceedings of the 27th ENMC sponsored workshop on congenital muscular dystrophy. 22\u201324 April 1994, The Netherlands","volume":"5","author":"Dubowitz","year":"1995","journal-title":"Neuromuscul Disord"},{"key":"B17","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1007\/BF02282889","article-title":"Congenital muscular dystrophy with laminin alpha 2 chain deficiency: identification of a new intermediate phenotype and correlation of clinical findings to muscle immunohistochemistry","volume":"155","author":"Herrmann","year":"1996","journal-title":"Eur J Pediatr"},{"key":"B18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1136\/jmg.34.2.99","article-title":"Refinement of the laminin alpha2 chain locus to human chromosome 6q2 in severe and mild merosin deficient congenital muscular dystrophy","volume":"34","author":"Naom","year":"1997","journal-title":"J Med Genet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1186\/s13023-021-01950-x","article-title":"Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort","volume":"16","author":"Tan","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"publisher","first-page":"741","DOI":"10.3390\/diagnostics10100741","article-title":"Whole exome sequencing as a diagnostic tool for unidentified muscular dystrophy in a Vietnamese family","volume":"10","author":"Nguyen","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.mcp.2013.11.002","article-title":"High creatine kinase levels and white matter changes: clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency","volume":"28","author":"Beyt\u00eda Mde","year":"2014","journal-title":"Mol Cell Probes"},{"key":"B23","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/mus.24588","article-title":"LAMA2-related myopathy: frequency among congenital and limb-girdle muscular dystrophies","volume":"52","author":"L\u00f8kken","year":"2015","journal-title":"Muscle Nerve"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1191068\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T10:14:10Z","timestamp":1687169650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1191068\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,19]]},"references-count":23,"alternative-id":["10.3389\/fped.2023.1191068"],"URL":"https:\/\/doi.org\/10.3389\/fped.2023.1191068","relation":{},"ISSN":["2296-2360"],"issn-type":[{"type":"electronic","value":"2296-2360"}],"subject":[],"published":{"date-parts":[[2023,6,19]]},"article-number":"1191068"}}