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Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies
Author(s) -
Nguyen Karine,
Bassez Guillaume,
Bernard Rafaëlle,
Krahn Martin,
Labelle Véronique,
FigarellaBranger Dominique,
Pouget Jean,
Hammouda El Hadi,
Béroud Christophe,
Urtizberea Andoni,
Eymard Bruno,
Leturcq France,
Lévy Nicolas
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9355
Subject(s) - dysferlin , biology , genetics , exon , coding region , gene , myopathy , limb girdle muscular dystrophy , mutation , phenotype , sequence analysis
DYSF encoding dysferlin is mutated in Miyoshi myopathy and Limb‐Girdle Muscular Dystrophy type 2B, the two main phenotypes recognized in dysferlinopathies. Dysferlin deficiency in muscle is the most relevant feature for the diagnosis of dysferlinopathy and prompts the search for mutations in DYSF . DYSF , located on chromosome 2p13, contains 55 coding exons and spans 150 kb of genomic DNA. We performed a genomic analysis of the DYSF coding sequence in 34 unrelated patients from various ethnic origins. All patients showed an absence or drastic decrease of dysferlin expression in muscle. A primary screening of DYSF using SSCP or dHPLC of PCR products of each of 55 exons of the gene was followed by sequencing whenever a sequence variation was detected. All together, 54 sequence variations were identified in DYSF , 50 of which predicting either a truncated protein or one amino‐acid substitution and most of them (34 out of 54) being novel. In 23 patients, we identified two pathogenic mutations, while only one was identified in 11 patients. These mutations were widely spread in the coding sequence of the gene without any mutational “hotspot.” © 2005 Wiley‐Liss, Inc.