Large proportion of XXXX cases in Sardinia due to a single founder mutation of the @entity529 gene.

@entity1 @entity72494 @entity19957 @entity746 @entity72493 @entity21 @entity529 @entity1367 @entity7104
OBJECTIVE: To perform an extensive screening for mutations of @entity746 ( @entity746 )-related genes in a consecutive cohort of Sardinian @entity1 , a genetic isolate phylogenically distinct from other European populations. DESIGN: Population-based, prospective cohort study. @entity1 : A total of 135 Sardinian @entity1 with @entity746 and 156 healthy control subjects of Sardinian origin who were age- and sex-matched to @entity1 . INTERVENTION: @entity1 underwent mutational analysis for @entity1367 , @entity19957 , and @entity529 . RESULTS: Mutational screening of the entire cohort found that 39 @entity1 (28.7%) carried the @entity72493 ( @entity72494 ) missense mutation of the @entity529 gene. Of these, 15 had @entity7104 (belonging to 10 distinct pedigrees) and 24 had apparently sporadic @entity746 . None of the 156 age-, sex-, and ethnicity-matched controls carried the pathogenic variant. Genotype data obtained for 5 @entity746 cases carrying the @entity72494 mutation found that they shared a 94-single-nucleotide polymorphism risk haplotype that spanned 663 Kb across the @entity529 locus on chromosome 1p36.22. Three @entity1 with @entity746 who carry the @entity72494 mutation developed @entity21 several years after their initial presentation with motor weakness. CONCLUSIONS: The @entity529 @entity72494 missense mutation accounts for approximately one-third of all @entity746 cases in this island population. These @entity1 share a large risk haplotype across the @entity529 locus, indicating that they have a common ancestor.
