Molecular Genetic Analysis of FOXL۲ Gene in Two Iranian Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

Background: Blepharophimosis-ptosis-epicanthus syndrome (BPES) is a rare genetic disorder with autosomal dominant inheritance.There are two distinct phenotypes: BPES type I, which is associated with eyelid abnormalities as well as female infertility orpremature menopause due to ovarian resistance to gonadotropins, whereas in type II only eyelid abnormalities are present. Mutationsin the forkhead transcription factor ۲ (FOXL۲) gene are responsible for both types of BPES.Objectives: The purpose of this study was to identify mutations in FOXL۲ in two Iranian families (from Tehran) with BPES who werereferred to Tehran Medical Genetics laboratory.Methods: The peripheral blood was collected from the affectedmembersof two BPES familiesandgenomicDNAwas extracted usingsalting out method. Then, direct sequencing of whole exon of FOXL۲ genewas performed.Results: Two frameshift mutations were identified in FOXL۲ gene in two familial cases including NM_۰۲۳۰۶۷:c.۱۰۲_۱۰۳insA(p.G۳۵Rfs*۶۱)as a novel mutation and NM_۰۲۳۰۶۷:c.۸۵۵_۸۷۱dup (p.H۲۹۱Rfs*۷۱) (۱۷-bp insertion). Both mutations cause the proteinto be truncated and are responsible for a severe phenotype (BPES type I) which was in harmony with our finding.Conclusions: Our results increased the spectrum of FOXL۲ mutations and confirm the mutations associated with BPES type I.

Keywords:

BPES , FOXL۲ , Premature Ovarian Failure , Eyelid Abnormalities