Novel mutations in the FOXC1 gene in Japanese patients withAxenfeld-Rieger syndrome

[摘要] Purpose: Mutations in the forkhead transcription factor (FOXC1)gene have been shown to cause juvenile glaucoma associated with avariety of anterior-segment anomalies. The purpose of this study was todetermine the ocular and genetic characteristics of two Japanesefamilies with Axenfeld-Rieger syndrome (ARS).Methods: Genomic DNA was extracted from the leukocytes of sixmembers of two families with ARS. The DNA from one exon of the FOXC1gene were amplified by polymerase chain reaction (PCR) and directlysequenced. The patients received standard systemic and ophthalmologicalexaminations.Results: Sequence analysis of the FOXC1 gene revealed a novelAla85Pro missense mutation in Helix1 in family 1 and a deletion of 17nucleotides (437-453) in Wing1 and Beta2 within the forkhead domain ofthe FOXC1 gene in family 2. This deletion predicted a loss of theforkhead domain by a premature termination of translation. Thesemutations segregated with the ARS phenotype in an autosomal dominantpattern. The affected individuals in family 1 had posterior embryotoxon,iris hypoplasia, corectopia with early-onset severe glaucoma, atrialseptal defect, aortic stenosis, and pulmonary stenosis. The affectedmembers in family 2 had posterior embryotoxon and iris hypoplasia withearly-onset glaucoma, and systemically they had hearing loss,hypertelorism, and telecanthus.Conclusions: A novel mutation in Helix1 and a novel deletion inWing1 and Beta2 of the forkhead domain of the FOXC1 gene have beenidentified in two families with ARS. FOXC1 mutations cause a varietyof developmental abnormalities in the anterior segment of the eye, andthey also induce an elevation in intraocular pressures and early-onsetglaucoma.

[学科分类] 生物化学/生物物理