title: Mutation spectrum of fork-head transcriptional factor gene (FOXL2) in Indian Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) patients.
abstract: OBJECTIVE
  The fork-head transcription factor gene (FOXL2) gene has been implicated in Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) type I and type II. The authors aimed to evaluate the involvement of FOXL2 in familial and sporadic cases of BPES in an Indian cohort.
  
  
  METHODS
  The present cohort comprised clinically well-characterised BPES cases that included six affected families, two sporadic cases and 60 unaffected normal controls. The 5' untranslated and coding region of FOXL2 was screened by resequencing and confirmed by restriction digestion. Further, genotype-phenotype correlations were done to understand the implications of the observed mutation.
  
  
  RESULTS
  Six mutations were observed in eight cases (87.5%). These included a novel deletion (c.860delC), three previously reported duplications (c.663-692dup 30, c.672-701dup30 and c.843-859dup17), a frame shift (c.804dupC) and a homozygous missense mutation (p.E69K). The p.E69k mutation was seen in both heterozygous and homozygous form in a large four-generational family, and disease severity was found to be directly linked to the allelic dosage. Two SNPs (c.501C→T, c.536C→G) were also noted. An unusual coexistence of polycystic ovarian disease (PCOD) with BPES was also seen in one of the families.
  
  
  CONCLUSIONS
  Mutations in the region downstream of the fork-head domain were predominantly responsible for BPES among Indian patients.
authors.affiliation: Hyderabad Eye Research Foundation, Hyderabad, India. inderjeet@lvpei.org
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Kaur
authors.forename: Avid
authors.initials: A
authors.lastname: Hussain
authors.forename: Milind N
authors.initials: MN
authors.lastname: Naik
authors.forename: Ramesh
authors.initials: R
authors.lastname: Murthy
authors.forename: Santosh G
authors.initials: SG
authors.lastname: Honavar
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D016569:Blepharophimosis / Q000235:genetics* / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005143:Eyelids / Q000002:abnormalities*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome; D055815:Young Adult
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors