{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:57:56Z","timestamp":1768463876149,"version":"3.49.0"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,4,1]]},"abstract":"<jats:p>LGMD (limb-girdle muscular dystrophy) and CMD (congenital muscular dystrophy) are two common forms of neuromuscular disorders which are distinguishable by their age of onset but with probably a similar underlying pathway. In the present study, we report immunohistochemical, Western-blot and genetic analyses in a large consanguineous Tunisian family with two branches, including seven patients sharing similar LGMD2 phenotype in one branch and one CMD patient in the other branch. Linkage analyses were compatible with the LGMD2A locus in one branch and the MDC1A (muscular dystrophy congenital type 1A) locus in the other branch. This result was supported by deficiency in merosin and calpain3 in the CMD patient and LGMD patients respectively. Mutation analysis revealed two distinct mutations: a c.8005delT frameshift deletion in exon 56 of the LAMA2 (laminin-\u03b12) gene (MDC1A) was found in the CMD patient and a new homozygous mutation c.1536+1G&amp;gt;T in the donor splice site of intron 12 of the CAPN3 (calpain3) gene (LGMD2A) was found in the LGMD patients. RT\u2013PCR (reverse transcription\u2013PCR) performed on total RNA from a LGMD2A patient's muscle biopsy showed complete retention of intron 12 in CAPN3 cDNA, generating a PTC (premature termination codon) that potentially elicits degradation of the nonsense mRNA by NMD (nonsense-mediated mRNA decay). Our results indicate that mRNA analysis is necessary to clarify the primary effect of genomic mutations on splicing efficiency that alters mRNA processing and expression level.<\/jats:p>","DOI":"10.1042\/bsr20100026","type":"journal-article","created":{"date-parts":[[2010,5,18]],"date-time":"2010-05-18T09:55:13Z","timestamp":1274176513000},"page":"125-135","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mutations in <i>LAMA2<\/i> and <i>CAPN3<\/i> genes associated with genetic and phenotypic heterogeneities within a single consanguineous family involving both congenital and progressive muscular dystrophies"],"prefix":"10.1042","volume":"31","author":[{"given":"Ikhlass","family":"Hadj\u00a0Salem","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire Humaine, Facult\u00e9 de M\u00e9decine de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"Kamoun","sequence":"additional","affiliation":[{"name":"Service de Neuro-p\u00e9diatrie, CHU H\u00e9di Chaker de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nacim","family":"Louhichi","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire Humaine, Facult\u00e9 de M\u00e9decine de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souad","family":"Rouis","sequence":"additional","affiliation":[{"name":"Biotech RDP, Centre de Biotechnologie de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam","family":"Mziou","sequence":"additional","affiliation":[{"name":"Service de Neuro-p\u00e9diatrie, CHU H\u00e9di Chaker de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nourhene","family":"Fendri-Kriaa","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire Humaine, Facult\u00e9 de M\u00e9decine de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"Makni-Ayadi","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie, CHU Habib Bourguiba de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chahnez","family":"Triki","sequence":"additional","affiliation":[{"name":"Service de Neuro-p\u00e9diatrie, CHU H\u00e9di Chaker de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiza","family":"Fakhfakh","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire Humaine, Facult\u00e9 de M\u00e9decine de Sfax, Sfax, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2010,11,23]]},"reference":[{"key":"2021111618073971300_B1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.nmd.2004.06.009","article-title":"The congenital muscular dystrophies in 2004: a century of exciting progress","volume":"14","author":"Muntoni","year":"2004","journal-title":"Neuromuscul. 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III"},{"key":"2021111618073971300_B5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.4103\/0028-3886.43445","article-title":"How to go about diagnosing and managing the limb-girdle muscular dystrophies","volume":"56","author":"Guglieri","year":"2008","journal-title":"Neurol. India"},{"key":"2021111618073971300_B6","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1093\/hmg\/8.5.855","article-title":"Dysferlin is a plasma membrane protein and is expressed early in human development","volume":"8","author":"Anderson","year":"1999","journal-title":"Hum. Mol. 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Disord."},{"key":"2021111618073971300_B15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1001\/jama.1963.03700150043007","article-title":"Management of progressive muscular dystrophy of childhood","volume":"194","author":"Vignos","year":"1963","journal-title":"J. Am. Med. Assoc."},{"key":"2021111618073971300_B16","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0022-510X(89)90223-2","article-title":"Dystrophin in skeletal muscle. Western blot analysis using a monoclonal antibody","volume":"94","author":"Nicholson","year":"1989","journal-title":"J. Neurol. 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Genet."},{"key":"2021111618073971300_B19","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1093\/brain\/awh408","article-title":"LGMD2A: genotype\u2013phenotype correlations based on a large mutational survey on the calpain 3 gene","volume":"128","author":"S\u00e1enz","year":"2005","journal-title":"Brain"},{"key":"2021111618073971300_B20","doi-asserted-by":"crossref","first-page":"e3750","DOI":"10.1371\/journal.pone.0003750","article-title":"Gene expression profiling in limb-girdle muscular dystrophy 2A","volume":"3","author":"S\u00e1enz","year":"2008","journal-title":"PLoS ONE"},{"key":"2021111618073971300_B21","first-page":"A436","article-title":"Calpain 3: characterization of the primary defect in LGMD2A and analysis of its secondary effect in other LGMDs","volume":"54","author":"Vainzof","year":"2000","journal-title":"Neurology"},{"key":"2021111618073971300_B22","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/j.1399-0004.2007.00906.x","article-title":"Transcriptional explorations of CAPN3 identify novel splicing mutations, a large-sized genomic deletion and evidence for messenger RNA decay","volume":"72","author":"Krahn","year":"2007","journal-title":"Clin. 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Genet."},{"key":"2021111618073971300_B31","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/brain\/119.1.295","article-title":"Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island","volume":"119","author":"Fardeau","year":"1996","journal-title":"Brain"},{"key":"2021111618073971300_B32","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0092-8674(93)90484-8","article-title":"Genetic identification of Mom-1, a major modifier locus affecting min-induced intestinal neoplasia in the mouse","volume":"75","author":"Dietrich","year":"1993","journal-title":"Cell"},{"key":"2021111618073971300_B33","first-page":"402","article-title":"Long mutant dystrophins and variable phenotypes: evasion of nonsensemediated decay? 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