Functional study on new FOXL2 mutations found in Chinese patients with blepharophimosis, ptosis, epicanthus inversus syndrome.
BACKGROUND
Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare inheritable disease that mainly affects eyelid development associated with (type I) or without (type II) ovarian dysfunction, resulting in premature ovarian failure (POF). Mutations in the gene forkhead box L2 (FOXL2) have been shown to be responsible for BPES. The aim of this study was to determine and functionally validate the FOXL2 mutation in a Chinese BPES family.


METHODS
Twelve individuals including five BPES patients from a Chinese family were enrolled. Genomic DNA was extracted from peripheral blood of enrolled subjects. The coding region of the FOXL2 gene was amplified and mutations were determined by sequencing analyses. Functional analysis was carried out to study changes in expression and transcriptional activity of the mutant FOXL2 protein.


RESULTS
A novel mutation in the FOXL2 gene (c.931C > T) was detected in all five BPES patients, which converts a histidine residue into a tyrosine (p.H311Y) in the FOXL2 protein. Functional analysis revealed that this point mutation reduces FOXL2 protein expression, concomitant with decreased transcriptional activity on the steroidogenic acute regulatory (StAR) gene promotor.


CONCLUSIONS
Our results expand the mutational spectrum of the FOXL2 gene and provide additional insights to the research on the molecular pathogenesis of FOXL2 in BPES.
['Zhou|Lu|L|', 'Wang|Jiaqi|J|', 'Wang|Tailing|T|0000-0002-3521-8400']
D044466:Asians D016569:Blepharophimosis D001763:Blepharoptosis D002460:Cell Line D045744:Cell Line, Tumor D005260:Female D000074842:Forkhead Box Protein L2 D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D008297:Male D009154:Mutation D010375:Pedigree D016649:Primary Ovarian Insufficiency D013577:Syndrome
FOXL2 BPES Gene mutation