可导致西班牙人临床多样性的DYSF基因新突变得到证实  

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

作　　者：Vilchez J.J. Gallano P. Gallardo E. I. Illa 高中宝 

机构地区：[1]Dr. Department of Neurology, Hospital Universitari de la Santa Creu I Sant Pau, Av Pare Claret, 167, 08025 Barcelona, Spain

出　　处：《世界核心医学期刊文摘（神经病学分册）》2005年第12期13-13,共1页Digest of the World Core Medical Journals:Clinical Neurology

摘　　要：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. Abstract: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.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. Abstract: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.

关 键 词：DYSF基因 代谢性肌病 基因突变 肌营养不良 肌肉活检标本 西班牙人 单链构型多态性 直接测序法 DNA 纯合子 

分 类 号：R746[医药卫生—神经病学与精神病学]