RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa
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 ana...
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doaj-2936ac7bb0374e2c93d4d53e177729712020-11-25T00:22:34ZengHindawi LimitedJournal of Ophthalmology2090-004X2090-00582014-01-01201410.1155/2014/210947210947RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis PigmentosaSatoshi Katagiri0Takaaki Hayashi1Masakazu Akahori2Takeshi Itabashi3Jo Nishino4Kazutoshi Yoshitake5Masaaki Furuno6Kazuho Ikeo7Tetsuji Okada8Hiroshi Tsuneoka9Takeshi Iwata10Division 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, JapanDepartment of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, JapanDivision 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, JapanDepartment of Life Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, JapanLaboratory of DNA Data Analysis, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, JapanLaboratory of DNA Data Analysis, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, JapanRIKEN 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, JapanLaboratory of DNA Data Analysis, National Institute of Genetics, 1111 Yata Mishima, Shizuoka 411-8540, JapanDepartment of Life Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, JapanDepartment of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, JapanDivision 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, JapanPurpose. 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.http://dx.doi.org/10.1155/2014/210947 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Satoshi Katagiri Takaaki Hayashi Masakazu Akahori Takeshi Itabashi Jo Nishino Kazutoshi Yoshitake Masaaki Furuno Kazuho Ikeo Tetsuji Okada Hiroshi Tsuneoka Takeshi Iwata |
spellingShingle |
Satoshi Katagiri Takaaki Hayashi Masakazu Akahori Takeshi Itabashi Jo Nishino Kazutoshi Yoshitake Masaaki Furuno Kazuho Ikeo Tetsuji Okada Hiroshi Tsuneoka Takeshi Iwata RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa Journal of Ophthalmology |
author_facet |
Satoshi Katagiri Takaaki Hayashi Masakazu Akahori Takeshi Itabashi Jo Nishino Kazutoshi Yoshitake Masaaki Furuno Kazuho Ikeo Tetsuji Okada Hiroshi Tsuneoka Takeshi Iwata |
author_sort |
Satoshi Katagiri |
title |
RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa |
title_short |
RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa |
title_full |
RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa |
title_fullStr |
RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa |
title_full_unstemmed |
RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa |
title_sort |
rho mutations (p.w126l and p.a346p) in two japanese families with autosomal dominant retinitis pigmentosa |
publisher |
Hindawi Limited |
series |
Journal of Ophthalmology |
issn |
2090-004X 2090-0058 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2014/210947 |
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