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Juan J. Vilchez, MD; Pia Gallano, PhD; Eduard Gallardo, PhD; Adriana Lasa, PhD; Ricardo Rojas-García, MD; Alba Freixas, BSc; Noemí De Luna, BSc; Francesc Calafell, PhD; Teresa Sevilla, MD; Fernando Mayordomo, MD; Montserrat Baiget, PhD; Isabel Illa, MD

Arch Neurol. 2005;62:1256-1259.

Background  Mutations in the dysferlin (DYSF) gene cause 3 different phenotypes of muscular dystrophies: Miyoshi myopathy, limb-girdle muscular dystrophy type 2B, and distal anterior compartment myopathy.

Objective  To present the results of clinical and molecular analysis of 8 patients with dysferlinopathy from 5 unrelated families.

Design  Clinical assessment was performed with a standardized protocol. A muscle biopsy specimen was obtained and studied by immunohistochemistry. Genetic analysis was performed using single-stranded conformation polymorphism and direct sequencing of genomic DNA.

Results  All the patients presented the R1905X mutation in the DYSF gene in homozygosity, and the haplotype analysis at the DYSF locus revealed that it was a novel and founder mutation. A C-to-T transition at nucleotide position 6086 changes an arginine into a stop codon, leading to premature termination of translation. This mutation was expressed as 3 different clinical phenotypes (limb-girdle muscular dystrophy type 2B, Miyoshi distal myopathy, and distal anterior dysferlinopathy), but only 1 phenotype was found in the same family.

Conclusions  The new R1905X DYSF founder mutation produced the 3 possible dysferlinopathy phenotypes without intrafamilial heterogeneity. This homogeneous population in Sueca, Spain, should be helpful in studying the modifying factors responsible for the phenotypic variability.

Author Affiliations: Servicio de Neurología, Hospital Universitari La Fe, Valencia (Drs Vilchez, Sevilla, and Mayordomo); Serveis de Genètica (Drs Gallano, Lasa, and Baiget and Ms Freixas) and de Neurología (Drs Gallardo, Rojas-García, and Illa and Ms De Luna), Hospital Universitari de la Santa Creu i Sant Pau, Barcelona; and Unitat de Biologia Evolutiva, Facultat de Ciències Experimentals i de la Salut, Universitat Pompeu i Fabra, Barcelona (Dr Calafell), Spain.

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