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AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration

PURPOSE: To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. METHODS: Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals unde...

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Autores principales: Li, David, Jin, Chongfei, Jiao, Xiaodong, Li, Lin, Bushra, Tahmina, Naeem, Muhammad Asif, Butt, Nadeem H., Husnain, Tayyab, Sieving, Paul A., Riazuddin, Sheikh, Riazuddin, S. Amer, Hejtmancik, J. Fielding
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2014
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888496/
https://www.ncbi.nlm.nih.gov/pubmed/24426771
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author Li, David
Jin, Chongfei
Jiao, Xiaodong
Li, Lin
Bushra, Tahmina
Naeem, Muhammad Asif
Butt, Nadeem H.
Husnain, Tayyab
Sieving, Paul A.
Riazuddin, Sheikh
Riazuddin, S. Amer
Hejtmancik, J. Fielding
author_facet Li, David
Jin, Chongfei
Jiao, Xiaodong
Li, Lin
Bushra, Tahmina
Naeem, Muhammad Asif
Butt, Nadeem H.
Husnain, Tayyab
Sieving, Paul A.
Riazuddin, Sheikh
Riazuddin, S. Amer
Hejtmancik, J. Fielding
author_sort Li, David
collection PubMed
description PURPOSE: To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. METHODS: Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes. RESULTS: Genome-wide linkage scans yielded a lod score of 3.05 at θ=0 for D17S1832 and 3.82 at θ=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. CONCLUSIONS: The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families.
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spelling pubmed-38884962014-01-14 AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration Li, David Jin, Chongfei Jiao, Xiaodong Li, Lin Bushra, Tahmina Naeem, Muhammad Asif Butt, Nadeem H. Husnain, Tayyab Sieving, Paul A. Riazuddin, Sheikh Riazuddin, S. Amer Hejtmancik, J. Fielding Mol Vis Research Article PURPOSE: To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. METHODS: Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes. RESULTS: Genome-wide linkage scans yielded a lod score of 3.05 at θ=0 for D17S1832 and 3.82 at θ=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. CONCLUSIONS: The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families. Molecular Vision 2014-01-06 /pmc/articles/PMC3888496/ /pubmed/24426771 Text en Copyright © 2014 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/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, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Li, David
Jin, Chongfei
Jiao, Xiaodong
Li, Lin
Bushra, Tahmina
Naeem, Muhammad Asif
Butt, Nadeem H.
Husnain, Tayyab
Sieving, Paul A.
Riazuddin, Sheikh
Riazuddin, S. Amer
Hejtmancik, J. Fielding
AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
title AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
title_full AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
title_fullStr AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
title_full_unstemmed AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
title_short AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
title_sort aipl1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888496/
https://www.ncbi.nlm.nih.gov/pubmed/24426771
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