Genetic analysis of a five generation Indian family with BPES: Anovel missense mutation (p.Y215C)

[摘要] Purpose: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES)is a rare eye genetic disorder caused by mutations in the FOXL2 genelocated at chromosome 3q23. The purpose of the present study was tocarry out genetic analysis of BPES in a five-generation Indian family.Methods: Peripheral blood samples were obtained from individuals forgenomic DNA isolation. To determine the linkage of this family to theFOXL2 locus, haplotype analysis was carried out using microsatellitemarkers from the BPES candidate region. Five overlapping sets of primerswere used to amplify the entire coding region of the FOXL2 gene formutation detection. Allele-specific oligonucleotide hybridization (ASOH)analysis was carried out to determine segregation of the mutation in thefamily and to also determine if the mutation was present in 100ethnically matched normal control chromosomes.Results: Pedigree analysis suggested that BPES segregated in thisfamily as an autosomal dominant trait. Cytogenetic analysis in onepatient did not reveal any rearrangement. Haplotype analysis suggestedthat this family was linked to the FOXL2 locus on chromosome 3q23.DNA sequence analysis showed that the BPES phenotype in this family wascaused by a novel missense mutation, c.881A->G (p.Y215C).Conclusions: This study reports for the first time a novel missensemutation in a five-generation Indian family with BPES. A review of theliterature showed that the total number of mutations in the FOXL2gene described to date is 42.

[学科分类] 生物化学/生物物理