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Prevalence of Mutations in Nine Candidate Genes in Japanese Patients with Autosomal Dominant Retinitis Pigmentosa

¹ Ophthalmology, Thohoku University School of Medicine, Sendai, Japan
² Ophthalmology, Kyushu University School of Medicine, Fukuoka, Japan
³ Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan

Commercial Relationships: Y. Wada, None; H. Sato, None; T. Itabashi, None; M. Kawamura, None; Y. Noda, None; M. Nakamura, None; T. Ishibashi, None; M. Tamai, None.

Grant Identification: none

Abstract

Purpose: To determine the type and prevalence of mutations in 9 genes (rodopsin, peripherin/RDS, RP1, NRL, FSCN2, PRPF31, PRPC8, HPRP3,and IMPDH1) in Japanese patients with autosomal dominant retinitis pigmentosa (ADRP), and to correlate the genotype to the phenotype.

Methods: The coding sequence and the adjacent flanking intron sequences of all exons of the 9 genes were directly sequenced in 96 unrelated patients with ADRP. The clinical features were characterized by visual acuity, slit–lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing.

Results: 16 causative mutations were found in 20 of the 96 patients with ADRP (20%). The prevalence of the causative mutations in the 9 genes were: rodopsin, 2.5%; peripherin/RDS, 5.2%; RP1, 1%; NRL, 0%; FSCN2, 4%; PRPF31, 4%; PRPC8, 0%; HPRP3, 1%; and IMPDH1, 2%. Among these, the Pro347Leu, Glu181Lys and Ser127Phe mutations in the rhodopsin gene, the Thr494Met mutation in the HPRP3 gene, and the IVS6–3to45del in the PRPF31 gene were common mutations in both the Japanese and foreign populations, and the others were novel. The ophthalmic findings in patients with mutations in the RP1and HPRP3 genes were typical retinitis pigmentosa with rapid progression over 40 years. Mutations in the PRPF31and FSCN2 genes show incomplete penetrance, which indicate the existence of asymptomatic patients.

Conclusions: The causative mutations in these 9 genes accounts for approximately 20% of cases with ADRP in Japan. The common mutations of Pro23His mutation in rhodopsin, Arg677X mutation in RP1, and Asp226Asn mutation in IMPDH1 genes were not detected in our patients. These findings suggested that the types and prevalence of mutations depend on the ethnic population.

Keywords: candidate gene analysis • retinal degenerations: hereditary • mutations

© 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.