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

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

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

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. ©2005 American Medical Association. All rights reserved.
Original languageEnglish
Pages (from-to)1256-1259
JournalArchives of Neurology
Volume62
Issue number8
DOIs
Publication statusPublished - 1 Aug 2005

Fingerprint Dive into the research topics of 'Identification of a novel founder mutation in the DYSF gene causing clinical variability in the spanish population'. Together they form a unique fingerprint.

  • Cite this

    Vilchez, J. J., Gallano, P., Gallardo, E., Lasa, A., Rojas-García, R., Freixas, A., De Luna, N., Calafell, F., Sevilla, T., Mayordomo, F., Baiget, M., & Illa, I. (2005). Identification of a novel founder mutation in the DYSF gene causing clinical variability in the spanish population. Archives of Neurology, 62(8), 1256-1259. https://doi.org/10.1001/archneur.62.8.1256