[Mutation analysis of FOXL2 gene and its structure protein in patients of blepharophimosis-ptosis-epicanthus inversus syndrome].

Abstract

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.

CONCLUSION:

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.

• Authors: Li-Xin Lin, Sheng-Jian Tang, Xiao-Ke Wang, Yan Sun, Yan-Li Wang
• Journal: [Zhonghua yan ke za zhi] Chinese journal of ophthalmology (Zhonghua Yan Ke Za Zhi) Vol. 43 Issue 6 Pg. 535-9 (Jun 2007) ISSN: 0412-4081 [Print] China
• PMID: 17897532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXL2 protein, human
• Forkhead Box Protein L2
• Forkhead Transcription Factors

Topics

• Amino Acid Sequence
• Blepharophimosis (genetics)
• DNA Mutational Analysis
• Female
• Forkhead Box Protein L2
• Forkhead Transcription Factors (genetics)
• Humans
• Male
• Molecular Sequence Data
• Mutation
• Pedigree
• Protein Structure, Secondary