Identification of a novel FOXL2 mutation in a single family with both types of blepharophimosis‑-ptosis-epicanthus inversus syndrome.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease, which has been divided into two types according to whether it involves premature ovarian failure (POF). Mutations in forkhead box L2 (FOXL2) have been identified in the majority of patients with BPES. The present study aimed to identify the causative mutation in FOXL2 in a Chinese family with both types of BPES. Clinical data and genomic DNA were collected from a single Chinese family with BPES. All the coding exons and adjacent regions of FOXL2 were screened in one affected member to detect the causative mutation using Sanger sequencing. The detected mutation was also screened in available family members and in 100 normal control chromosomes. In total, seven family members were recruited in the present study, including four affected and three unaffected members. The patient (II:5) exhibited typical features of type II BPES, characterized by a narrowed horizontal palpehral aperture, ptosis, epicanthus inversus and telecanthus without POF, whereas the patient's three daughters (III:1, III:2 and III:3) were diagnosed with type I BPES, in which a complex eyelid malformation was accompanied with POF. A novel heterozygous mutation in FOXL2 (c.844_860dup17, p.His291Argfs*71) was found in the four affected members, which was absent in the remaining three unaffected members and in the 100 control chromosomes. This novel duplicate mutation (c.844_860dup17, p.His291Argfs*71) in FOXL2 was identified in a Chinese family with both types of BPES. These findings expand current knowledge of the mutation spectrum of the FOXL2 gene and confirmed the intra‑family phenotypic heterogeneity of BPES.