Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies.
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."
Nguyen
Karine
K
Département de Génétique Médicale, Hôpital d'enfants de la Timone, Marseille, France.
Bassez
Guillaume
G
Bernard
Rafaëlle
R
Krahn
Martin
M
Labelle
Véronique
V
Figarella-Branger
Dominique
D
Pouget
Jean
J
Hammouda
El Hadi
el H
Béroud
Christophe
C
Urtizberea
Andoni
A
Eymard
Bruno
B
Leturcq
France
F
Lévy
Nicolas
N
D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008957:Models, Genetic; D009124:Muscle Proteins / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins