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A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family

PURPOSE: The purpose of this study was to identify the underlying molecular genetic defect in a large consanguineous Pakistani family with Oguchi disease who had been given a diagnosis of autosomal recessive retinitis pigmentosa. METHODS: The family was genotyped with the Affymetrix 10K single nucle...

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Autores principales: Azam, Maleeha, Collin, Rob W.J., Khan, Muhammad Imran, Shah, Syed Tahir Abbas, Qureshi, Nadeem, Ajmal, Muhammad, den Hollander, Anneke I., Qamar, Raheel, Cremers, Frans P.M.
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742643/
https://www.ncbi.nlm.nih.gov/pubmed/19753316
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author Azam, Maleeha
Collin, Rob W.J.
Khan, Muhammad Imran
Shah, Syed Tahir Abbas
Qureshi, Nadeem
Ajmal, Muhammad
den Hollander, Anneke I.
Qamar, Raheel
Cremers, Frans P.M.
author_facet Azam, Maleeha
Collin, Rob W.J.
Khan, Muhammad Imran
Shah, Syed Tahir Abbas
Qureshi, Nadeem
Ajmal, Muhammad
den Hollander, Anneke I.
Qamar, Raheel
Cremers, Frans P.M.
author_sort Azam, Maleeha
collection PubMed
description PURPOSE: The purpose of this study was to identify the underlying molecular genetic defect in a large consanguineous Pakistani family with Oguchi disease who had been given a diagnosis of autosomal recessive retinitis pigmentosa. METHODS: The family was genotyped with the Affymetrix 10K single nucleotide polymorphism array. Fine-mapping of a common homozygous region on chromosome 13q was performed using fluorescent microsatellite markers. Mutation analysis was done by direct sequencing of the candidate gene GRK1 located in the region. The segregation of a novel mutation in the family and the frequency of the identified mutation in the Pakistani population were determined by StuI RFLP analysis. RESULTS: Genetic mapping supported the diagnosis of typical Oguchi disease in a Pakistani family and also resulted in the identification of a novel nonsense mutation (c.614C>A; p.S205X) in exon 1 of GRK1. This mutation is predicted to result in premature termination of the protein product, thereby affecting the phototransduction cascade. A clinical reappraisal of the family revealed that all patients homozygous for this variant had Oguchi disease. CONCLUSIONS: This is the first report to describe a mutation causing typical Oguchi disease in a large consanguineous Pakistani family. This mutation segregated in eight affected members.
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spelling pubmed-27426432009-09-14 A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family Azam, Maleeha Collin, Rob W.J. Khan, Muhammad Imran Shah, Syed Tahir Abbas Qureshi, Nadeem Ajmal, Muhammad den Hollander, Anneke I. Qamar, Raheel Cremers, Frans P.M. Mol Vis Research Article PURPOSE: The purpose of this study was to identify the underlying molecular genetic defect in a large consanguineous Pakistani family with Oguchi disease who had been given a diagnosis of autosomal recessive retinitis pigmentosa. METHODS: The family was genotyped with the Affymetrix 10K single nucleotide polymorphism array. Fine-mapping of a common homozygous region on chromosome 13q was performed using fluorescent microsatellite markers. Mutation analysis was done by direct sequencing of the candidate gene GRK1 located in the region. The segregation of a novel mutation in the family and the frequency of the identified mutation in the Pakistani population were determined by StuI RFLP analysis. RESULTS: Genetic mapping supported the diagnosis of typical Oguchi disease in a Pakistani family and also resulted in the identification of a novel nonsense mutation (c.614C>A; p.S205X) in exon 1 of GRK1. This mutation is predicted to result in premature termination of the protein product, thereby affecting the phototransduction cascade. A clinical reappraisal of the family revealed that all patients homozygous for this variant had Oguchi disease. CONCLUSIONS: This is the first report to describe a mutation causing typical Oguchi disease in a large consanguineous Pakistani family. This mutation segregated in eight affected members. Molecular Vision 2009-09-05 /pmc/articles/PMC2742643/ /pubmed/19753316 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of 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
Azam, Maleeha
Collin, Rob W.J.
Khan, Muhammad Imran
Shah, Syed Tahir Abbas
Qureshi, Nadeem
Ajmal, Muhammad
den Hollander, Anneke I.
Qamar, Raheel
Cremers, Frans P.M.
A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family
title A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family
title_full A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family
title_fullStr A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family
title_full_unstemmed A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family
title_short A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family
title_sort novel mutation in grk1 causes oguchi disease in a consanguineous pakistani family
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742643/
https://www.ncbi.nlm.nih.gov/pubmed/19753316
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