title: Genetic analysis of the forkhead transcriptional factor 2 gene in three Chinese families with blepharophimosis syndrome.
abstract: OBJECTIVE
  Clinically, blepharophimosis syndrome (BPES) has been divided into two subsets according to the association of ocular malformation with (type I) or without (type II) premature ovarian failure (POF). BPES is ascribed to mutations in the forkhead transcriptional factor 2 (FOXL2) gene. This study aimed at identifying clinical features and mutations within the FOXL2 gene in three Chinese families with BPES.
  
  
  METHODS
  A clinical and molecular genetic investigation was performed in affected and unaffected members from three Chinese families with BPES. Genomic DNA was prepared from leucocytes of peripheral venous blood, the entire coding region of FOXL2 were amplified with PCR, and direct DNA sequencing of the PCR products was performed for mutations in FOXL2.
  
  
  RESULTS
  Three mutations in FOXL2 were found in three families, including c.672_701dup30, c.663_692dup30, and c.475dupC. Of the three, the c.475dupC (p.His159fs) was novel in family C and resulted in a frameshift mutation to generate a truncated protein owing to a premature stop codon at codon 238. The new duplication mutation was associated with BPES type II. The c.672_701dup30 (p.Ala224_Ala234dup10) and the c.663_692dup30 (p.Ala221_Ala231dup10) were detected in family A and family B, respectively, leading to expansions of the polyalanine (poly-Ala) tract that is frequently the hot spot of mutations within FOXL2.
  
  
  CONCLUSIONS
  Our results expand the spectrum of FOXL2 mutations, and further indicate the association of a novel duplication mutation leading to a truncated protein with BPES type II. The other two known mutations may support the previous hypothesis regarding expansions of the polyalanine tract associated with BPES type II as a mutational hot spot in FOXL2.
authors: Molecular Medicine Research Center, West China Hospital, Sichuan University, Chengdu, PR China.
authors: Haiou
authors: H
authors: Jiang
authors: Xueshuang
authors: X
authors: Huang
authors: Zhiguang
authors: Z
authors: Su
authors: Libing
authors: L
authors: Rao
authors: Sisi
authors: S
authors: Wu
authors: Ting
authors: T
authors: Zhang
authors: Kang
authors: K
authors: Li
authors: Qingli
authors: Q
authors: Quan
authors: Kang
authors: K
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016569:Blepharophimosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D017124:Conserved Sequence; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D012868:Skin Abnormalities / Q000235:genetics*; D055815:Young Adult
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors