title: Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients.
abstract: Bleparophimosis ptosis epicanthus inversus syndrome (BPES) is a rare disorder characterized by eyelid malformation and in some cases associated with premature ovarian failure. Although the familial form is autosomal dominant, many cases are also sporadic. The mutations causing this disorder were found in a winged/forkhead transcription factor gene named FOXL2. We have sequenced the mouse homolog for the FOXL2 gene and identified the Fugu rubripes (pufferfish) ortholog from the database. By alignment of the three sequences, we found an almost complete conservation of the forkhead domain in the three species. There is 95% and 61% conservation at the protein level between human-mouse and human-pufferfish, respectively. The polyalanine and polyproline tracts within the gene are absent in Fugu rubripes. An overview identifies four breaks in the conservation of the gene within these species. Using a direct sequencing approach, we performed mutation analysis from DNA of nine affected individuals from familial and sporadic cases. The mutations are distributed throughout the coding region of the FOXL2 gene. We identified five novel mutations: g.292delG (E19fsX149); g.530G>A (W98X); g.548A>G (H104R); g.652G>T (E139X); and g.1178_1185del8 (A314fsX530). In addition we also identified two known mutations g.823C>T (Q196X) and g.1092_1108dup17, the latter in individuals from three unrelated pedigrees.
authors.affiliation: Jules Stein Eye Institute, University of California, Los Angeles, California 90095, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
authors.forename: Vivek
authors.initials: V
authors.lastname: Yellore
authors.forename: Meenal
authors.initials: M
authors.lastname: Chalukya
authors.forename: Svetlana
authors.initials: S
authors.lastname: Yelchits
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Silva-Garcia
authors.forename: Kent
authors.initials: K
authors.lastname: Small
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D016569:Blepharophimosis / Q000235:genetics*; D001763:Blepharoptosis / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009154:Mutation; D010053:Ovary / Q000002:abnormalities; D010375:Pedigree; D013577:Syndrome; D023741:Takifugu / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D014157:Transcription Factors