[Mutation analysis of FOXL2 gene and its structure protein in patients of blepharophimosis-ptosis-epicanthus inversus syndrome].
OBJECTIVE
The aim of this study was to investigate the effect of mutations of the forkhead transcription factor 2 (FOXL2) gene on the primary and secondary structure of the coded protein and seek for the molecular mechanism of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).


METHODS
The genomic DNA was extracted from peripheral blood of 7 clinically diagnosed BPES patients, PCR amplification of FOXL2 coding region and 5' untranslated region were performed. Sequence analysis was performed using the PCR or cloning products. The structure of the protein was predicted with PDH and ExPASy software, and the difference between the normal and the mutational protein was analyzed.


RESULTS
A 901- 930 dup 30 mutation of FOXL2 was found in two patients from a BPES family of type II and a sporadic case, and no any mutations were detected in normal control. Analysis of the primary structure displayed that the molecular weight of the protein coded by the mutated gene was greater than the normal, but both have the same isoelectric point. Analysis of the secondary structure showed that FOXL2 was a transmembrane protein with a polyalanine tract which contained a alpha-helix. When the polyalanine tract expanded, the helix region extended, as a result, the proportion of alpha-helix increased by 4.1%, but the proportions of beta-pleated sheet and random coil decreased correspondingly.


CONCLUSIONS
Our results suggest that the 901 - 930 dup 30 mutation of FOXL2 is a novel finding. Moreover, this mutation causes great changes in the primary and secondary structure of the coded protein, which may be the molecular pathogenesis of BPES.
Lin
Li-Xin
LX
Institute of Plastic Surgery, Weifang Medical College, Weifang 261042, China.
Tang
Sheng-Jian
SJ
Wang
Xiao-Ke
XK
Sun
Yan
Y
Wang
Yan-Li
YL
D000595:Amino Acid Sequence; D016569:Blepharophimosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017433:Protein Structure, Secondary
C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors