Format

Send to

Choose Destination
See comment in PubMed Commons below
Arch Neurol. 2005 Aug;62(8):1256-9.

Identification of a novel founder mutation in the DYSF gene causing clinical variability in the Spanish population.

Author information

1
Servicio de Neurología, Hospital Universitari La Fe, Valencia, Spain.

Abstract

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.

PMID:
16087766
DOI:
10.1001/archneur.62.8.1256
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Support Center