Identification and functional analyses of a novel pathogenic variant causing blepharophimosis, ptosis, and epicanthus inversus syndrome.

Aim: To discover the molecular pathogenic basis of the blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), and to predict the clinical subtype according to experiments, which is significant to the prognosis.

Methods: A 3-year-old sporadic female patient with typical clinical manifestations of BPES was enrolled. The coding region of forkhead box L2 () gene was sequenced, and the functional assays were performed by Western blotting, subcellular localization experiment, luciferase reporter assay, and quantitative real-time polymerase chain reaction.

Results: A novel point pathogenic variant (c.274G>T) was detected, resulting in a truncated protein (p.E92*). Functional studies demonstrated that the pathogenic variant induced the subcellular mislocalization and the abnormal transcriptional activity on promoters of the steroidogenic acute regulatory protein ( or ) gene and the odd-skipped related 2 transcription factor () gene.

Conclusion: A novel pathogenic variant is identified to expand the spectrum of the known mutations. The experiments provide reference data and more insights to the molecular pathogenesis of BPES. The predicted high risk of ovarian insufficiency makes it significant for the patient enrolled to have further follow-up and therapy concerning female endocrinology.