Background: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare, autosomal dominant disease. There are two clinical types of BPES: type I patients have eyelid abnormalities accompanied by infertility in affected females, while type II patients only display eyelid malformations. Previous studies have reported that the forkhead box L2 (FOXL2) gene mutations cause BPES.
Purpose: To identify plausible FOXL2 mutation in a Chinese family with BPES and infertility METHODS: Mutational screening of FOXL2 was performed in the affected members and 223 controls. Functional characterization of the novel mutation identified was carried out in vitro by luciferase reporter assay and subcellular localization experiment.
Results: A novel heterozygous mutation c.188 T > A (p.I63N) in FOXL2 was identified in two BPES patients in this family. The mutation abolished the transcriptional repression of FOXL2 on the promoters of CYP19A1 and CCND2 genes, as shown by luciferase reporter assays. However, no dominant-negative effect was observed for the mutation, and it did not impact FOXL2 protein nuclear localization and distribution.
Conclusions: The mutation c.188 T > A (p.I63N) in FOXL2 might be causative for BPES and infertility in this family and further amplified the spectrum of FOXL2 mutations.
Keywords: Blepharophimosis–ptosis–epicanthus inversus syndrome; FOXL2; Infertility; Mutation.