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Y. Wada, T. Itabashi, M. Sukegawa, A. Tada, H. Sato, E. Imai, K. Nishida; Prevalence of Mutations in Seven Candidate Genes in Japanese Patients With Leber`s Congenital Amaurosis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1691.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the type and prevalence of mutations in 7 genes (RPE65, CRX, LRAT, GUCY2D, CRB1, AIPL1 and RDH12), in Japanese patients with Leber’s congenital amaurosis (LCA), and to correlate the genotype to the phenotype.
The coding sequence and the adjacent flanking intron sequences of all exons of the 7 genes were directly sequenced in72 unrelated patients with LCA. The clinical features were characterized by visual acuity, slit–lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing.
6 causative mutations were found in 3of the 72 patients with LCA (4%). The compound heterozygous Arg515Trp and Arg124X in the RPE65 gene, the Leu154Pro and 733–735delGAG mutations in the AIPL1 gene, and the Lys192X and Gln161Trp mutations in the RDH12 gene cosegregated with the phenotype in Japanese patients with LCA. The heterozygous Arg515Trp mutation in the RPE65 gene was found in three unrelated patients with LCA, however, sequencing of the entire gene did not reveal a 2nd mutant allele. The prevalence of the causative mutations in the 7 genes were: RPE65, 1.4%; CRX, 0%; LRAT, 0%; GUCY2D, 0%; CRB1, 0%; AIPL1,1.4%; and RDH12, 1.4%. Among these mutations,, the Leu154Pro and 733–735delGAG mutations in the AIPL1 gene, and the Lys192X and Gln161Trp mutations in the RDH12 gene were novel mutations. Nyctalopia was observed with RPE65, AIPL1 and RDH12, nystagmus with AIPL1 sequence variants. The visual acuity ranged from 0.2 to light perception. Patients associated with AIPL1 mutations showed not only severe retinal degeneration but also keratoconus in the both eyes. Twenty year clinical follow–up of two siblings associated with RPE65 mutations disclosed that the progression of retinal degeneration was relatively slow and peripheral visual field was preserved.
The causative mutations in these 7 genes accounts for approximately 4% of cases with LCA in Japan. Also our study demonstrated that mutations in the RPE65, RDH12 and AIPL1 gene caused Japanese patients with LCA, although the types and prevalence of mutations depend on the ethnic population.
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