Cargando…

Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa

PURPOSE: This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. METHODS: Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected i...

Descripción completa

Detalles Bibliográficos
Autores principales: Ali, Shahbaz, Riazuddin, S. Amer, Shahzadi, Amber, Nasir, Idrees A., Khan, Shaheen N., Husnain, Tayyab, Akram, Javed, Sieving, Paul A., Hejtmancik, J. Fielding, Riazuddin, Sheikh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108895/
https://www.ncbi.nlm.nih.gov/pubmed/21655355
_version_ 1782205379808067584
author Ali, Shahbaz
Riazuddin, S. Amer
Shahzadi, Amber
Nasir, Idrees A.
Khan, Shaheen N.
Husnain, Tayyab
Akram, Javed
Sieving, Paul A.
Hejtmancik, J. Fielding
Riazuddin, Sheikh
author_facet Ali, Shahbaz
Riazuddin, S. Amer
Shahzadi, Amber
Nasir, Idrees A.
Khan, Shaheen N.
Husnain, Tayyab
Akram, Javed
Sieving, Paul A.
Hejtmancik, J. Fielding
Riazuddin, Sheikh
author_sort Ali, Shahbaz
collection PubMed
description PURPOSE: This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. METHODS: Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the β subunit of phosphodiesterase 6 (PDE6β) was completed. RESULTS: During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP. Sequencing of PDE6β identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein. CONCLUSIONS: These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families.
format Online
Article
Text
id pubmed-3108895
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Molecular Vision
record_format MEDLINE/PubMed
spelling pubmed-31088952011-06-07 Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa Ali, Shahbaz Riazuddin, S. Amer Shahzadi, Amber Nasir, Idrees A. Khan, Shaheen N. Husnain, Tayyab Akram, Javed Sieving, Paul A. Hejtmancik, J. Fielding Riazuddin, Sheikh Mol Vis Research Article PURPOSE: This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. METHODS: Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the β subunit of phosphodiesterase 6 (PDE6β) was completed. RESULTS: During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP. Sequencing of PDE6β identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein. CONCLUSIONS: These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families. Molecular Vision 2011-05-25 /pmc/articles/PMC3108895/ /pubmed/21655355 Text en Copyright © 2011 Molecular Vision. 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
Ali, Shahbaz
Riazuddin, S. Amer
Shahzadi, Amber
Nasir, Idrees A.
Khan, Shaheen N.
Husnain, Tayyab
Akram, Javed
Sieving, Paul A.
Hejtmancik, J. Fielding
Riazuddin, Sheikh
Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa
title Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa
title_full Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa
title_fullStr Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa
title_full_unstemmed Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa
title_short Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa
title_sort mutations in the β-subunit of rod phosphodiesterase identified in consanguineous pakistani families with autosomal recessive retinitis pigmentosa
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108895/
https://www.ncbi.nlm.nih.gov/pubmed/21655355
work_keys_str_mv AT alishahbaz mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT riazuddinsamer mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT shahzadiamber mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT nasiridreesa mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT khanshaheenn mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT husnaintayyab mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT akramjaved mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT sievingpaula mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT hejtmancikjfielding mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa
AT riazuddinsheikh mutationsinthebsubunitofrodphosphodiesteraseidentifiedinconsanguineouspakistanifamilieswithautosomalrecessiveretinitispigmentosa