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

PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare eye genetic disorder caused by mutations in the FOXL2 gene located at chromosome 3q23. The purpose of the present study was to carry out genetic analysis of BPES in a five-generation Indian family.
METHODS: Peripheral blood samples were obtained from individuals for genomic DNA isolation. To determine the linkage of this family to the FOXL2 locus, haplotype analysis was carried out using microsatellite markers from the BPES candidate region. Five overlapping sets of primers were used to amplify the entire coding region of the FOXL2 gene for mutation detection. Allele-specific oligonucleotide hybridization (ASOH) analysis was carried out to determine segregation of the mutation in the family and to also determine if the mutation was present in 100 ethnically matched normal control chromosomes.
RESULTS: Pedigree analysis suggested that BPES segregated in this family as an autosomal dominant trait. Cytogenetic analysis in one patient did not reveal any rearrangement. Haplotype analysis suggested that this family was linked to the FOXL2 locus on chromosome 3q23. DNA sequence analysis showed that the BPES phenotype in this family was caused by a novel missense mutation, c.881A->G (p.Y215C).
CONCLUSIONS: This study reports for the first time a novel missense mutation in a five-generation Indian family with BPES. A review of the literature showed that the total number of mutations in the FOXL2 gene described to date is 42.