title: Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25.
abstract: Mutations in the forkhead-like 7 (FKHL7) gene have been recently shown to cause juvenile glaucoma and anterior segment anomalies. We report on a three-generation family with Axenfeld-Rieger syndrome (ARS), harboring an alteration in the FKHL7 gene. Genetic linkage analyses excluded the ARS phenotype from chromosomes 4q25 and 13q14, the locations of the PITX2 and RIEG2 loci, respectively. Evidence of linkage was observed with markers at 6p25, near the FKHL7 gene. Direct sequencing of FKHL7 detected a C67T mutation that segregated with the ARS phenotype in this family, but was not detected in over 80 control chromosomes. This mutation is predicted to cause a nonsense mutation of the FKHL7 protein (Gln23Stop) upstream of the forkhead DNA-binding domain, and thus to generate a truncated FKHL7 protein product. This discovery broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.
authors.affiliation: Department of Ophthalmology, University of Alberta, Edmonton, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Mirzayans
authors.forename: D B
authors.initials: DB
authors.lastname: Gould
authors.forename: E
authors.initials: E
authors.lastname: Héon
authors.forename: G D
authors.initials: GD
authors.lastname: Billingsley
authors.forename: J C
authors.initials: JC
authors.lastname: Cheung
authors.forename: A J
authors.initials: AJ
authors.lastname: Mears
authors.forename: M A
authors.initials: MA
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D000869:Anterior Eye Segment / Q000002:abnormalities; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D008040:Genetic Linkage; D005838:Genotype; D005901:Glaucoma / Q000151:congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors