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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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Autores principales: Katagiri, Satoshi, Hayashi, Takaaki, Akahori, Masakazu, Itabashi, Takeshi, Nishino, Jo, Yoshitake, Kazutoshi, Furuno, Masaaki, Ikeo, Kazuho, Okada, Tetsuji, Tsuneoka, Hiroshi, Iwata, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248368/
https://www.ncbi.nlm.nih.gov/pubmed/25485142
http://dx.doi.org/10.1155/2014/210947
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author Katagiri, Satoshi
Hayashi, Takaaki
Akahori, Masakazu
Itabashi, Takeshi
Nishino, Jo
Yoshitake, Kazutoshi
Furuno, Masaaki
Ikeo, Kazuho
Okada, Tetsuji
Tsuneoka, Hiroshi
Iwata, Takeshi
author_facet Katagiri, Satoshi
Hayashi, Takaaki
Akahori, Masakazu
Itabashi, Takeshi
Nishino, Jo
Yoshitake, Kazutoshi
Furuno, Masaaki
Ikeo, Kazuho
Okada, Tetsuji
Tsuneoka, Hiroshi
Iwata, Takeshi
author_sort Katagiri, Satoshi
collection PubMed
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.
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spelling pubmed-42483682014-12-07 RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa Katagiri, Satoshi Hayashi, Takaaki Akahori, Masakazu Itabashi, Takeshi Nishino, Jo Yoshitake, Kazutoshi Furuno, Masaaki Ikeo, Kazuho Okada, Tetsuji Tsuneoka, Hiroshi Iwata, Takeshi J Ophthalmol Research Article 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. Hindawi Publishing Corporation 2014 2014-11-16 /pmc/articles/PMC4248368/ /pubmed/25485142 http://dx.doi.org/10.1155/2014/210947 Text en Copyright © 2014 Satoshi Katagiri et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Katagiri, Satoshi
Hayashi, Takaaki
Akahori, Masakazu
Itabashi, Takeshi
Nishino, Jo
Yoshitake, Kazutoshi
Furuno, Masaaki
Ikeo, Kazuho
Okada, Tetsuji
Tsuneoka, Hiroshi
Iwata, Takeshi
RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248368/
https://www.ncbi.nlm.nih.gov/pubmed/25485142
http://dx.doi.org/10.1155/2014/210947
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