title: Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma.
abstract: The forkhead transcription factor gene FOXC1 (formerly FKHL7) is responsible for a number of glaucoma phenotypes in families in which the disease maps to 6p25, although mutations have not been found in all families in which the disease maps to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to 6p25 (peak LOD score 6.20 [recombination fraction 0] at D6S967), no FOXC1 mutations were detected by direct sequencing. However, genotyping with microsatellite repeat markers suggested the presence of a chromosomal duplication that segregated with the disease phenotype. The duplication was confirmed in affected individuals by FISH with markers encompassing FOXC1. These results provide evidence of gene duplication causing developmental disease in humans, with increased gene dosage of either FOXC1 or other, as yet unknown genes within the duplicated segment being the probable mechanism responsible for the phenotype.
authors.affiliation: Department of Molecular Genetics, Institute of Ophthalmology, London, England EC1V 9EL. OJLehmann@yahoo.com
authors.forename: O J
authors.initials: OJ
authors.lastname: Lehmann
authors.forename: N D
authors.initials: ND
authors.lastname: Ebenezer
authors.forename: T
authors.initials: T
authors.lastname: Jordan
authors.forename: M
authors.initials: M
authors.lastname: Fox
authors.forename: L
authors.initials: L
authors.lastname: Ocaka
authors.forename: A
authors.initials: A
authors.lastname: Payne
authors.forename: B P
authors.initials: BP
authors.lastname: Leroy
authors.forename: B J
authors.initials: BJ
authors.lastname: Clark
authors.forename: R A
authors.initials: RA
authors.lastname: Hitchings
authors.forename: S
authors.initials: S
authors.lastname: Povey
authors.forename: P T
authors.initials: PT
authors.lastname: Khaw
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005260:Female; D051858:Forkhead Transcription Factors; D020440:Gene Duplication; D005901:Glaucoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007498:Iris / Q000378:metabolism / Q000473:pathology*; D008126:Lod Score; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors