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

Arch Neurol. 2005 Aug;62(8):1256-9. doi: 10.1001/archneur.62.8.1256.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Codon, Nonsense / genetics
  • DNA Mutational Analysis
  • Dysferlin
  • Female
  • Founder Effect*
  • Genetic Testing
  • Genetic Variation / genetics*
  • Haplotypes / genetics
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Muscle Proteins / genetics*
  • Muscular Dystrophies / ethnology
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / physiopathology
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Point Mutation / genetics
  • Spain


  • Codon, Nonsense
  • DYSF protein, human
  • Dysferlin
  • Membrane Proteins
  • Muscle Proteins