title: RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa.
abstract: Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP). Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling.
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan ; Department of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Satoshi
authors.identifier: 0000-0001-7787-8194
authors.initials: S
authors.lastname: Katagiri
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Takaaki
authors.identifier: 0000-0003-3269-8725
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Akahori
authors.affiliation: Department of Life Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Itabashi
authors.affiliation: Laboratory of DNA Data Analysis, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, Japan.
authors.forename: Jo
authors.initials: J
authors.lastname: Nishino
authors.affiliation: Laboratory of DNA Data Analysis, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Yoshitake
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Life Science Accelerator Technology Group, Transcriptome Technology Team, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Masaaki
authors.identifier: 0000-0002-8483-2941
authors.initials: M
authors.lastname: Furuno
authors.affiliation: Laboratory of DNA Data Analysis, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.affiliation: Department of Life Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Tetsuji
authors.identifier: 0000-0003-1913-428X
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
authors.forename: Takeshi
authors.identifier: 0000-0003-1447-0081
authors.initials: T
authors.lastname: Iwata