title: Mutations in FOXL2 underlying BPES (types 1 and 2) in Colombian families.
abstract: We report the genetic characterization of one family with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type 1 and two families with BPES type 2 from a historically isolated population in northwest Colombia. Linkage and haplotype analyses indicate that BPES in these families is linked to 3q23. Mutation screening of FOXL2 in the family with BPES type 1 revealed a novel 394C --> T nonsense mutation which deletes the forkhead DNA binding domain. The two families with BPES type 2 both carry an in-frame 30 bp duplication that leads to the elongation of a polyalanine tract. This duplication has been previously reported in Europe, where recurrent mutation has been demonstrated in unrelated familial and sporadic BPES cases. The recurrent nature of this duplication seems to relate to the secondary structure of this DNA region. The genotype-phenotype correlation seen in the Colombian families is consistent with the recent proposal that BPES type 1 is caused by truncating mutations leading to haploinsufficiency, while BPES type 2 is due to mutations generating elongated protein products.
authors.affiliation: Unidad de Genética Medica, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: J L
authors.initials: JL
authors.lastname: Ramírez-Castro
authors.forename: N
authors.initials: N
authors.lastname: Pineda-Trujillo
authors.forename: A V
authors.initials: AV
authors.lastname: Valencia
authors.forename: C M
authors.initials: CM
authors.lastname: Muñetón
authors.forename: O
authors.initials: O
authors.lastname: Botero
authors.forename: O
authors.initials: O
authors.lastname: Trujillo
authors.forename: G
authors.initials: G
authors.lastname: Vásquez
authors.forename: B E
authors.initials: BE
authors.lastname: Mora
authors.forename: N
authors.initials: N
authors.lastname: Durango
authors.forename: G
authors.initials: G
authors.lastname: Bedoya
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Linares
mesh_terms: D016569:Blepharophimosis / Q000235:genetics*; D001763:Blepharoptosis / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D003105:Colombia / Q000208:ethnology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005143:Eyelids / Q000002:abnormalities*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D014157:Transcription Factors