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Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome
BACKGROUND: EAST syndrome is an autosomal recessive disorder caused by loss‐of‐function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a res...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023937/ https://www.ncbi.nlm.nih.gov/pubmed/27652280 http://dx.doi.org/10.1002/mgg3.227 |
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author | Abdelhadi, Ola Iancu, Daniela Tekman, Mehmet Stanescu, Horia Bockenhauer, Detlef Kleta, Robert |
author_facet | Abdelhadi, Ola Iancu, Daniela Tekman, Mehmet Stanescu, Horia Bockenhauer, Detlef Kleta, Robert |
author_sort | Abdelhadi, Ola |
collection | PubMed |
description | BACKGROUND: EAST syndrome is an autosomal recessive disorder caused by loss‐of‐function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to establish the existence of a potential founder effect in the Pakistani population. METHODS: To this end, we genotyped 12 patients from seven families and we compared disease haplotypes with ethnically matched control chromosomes. This haplotype was used together with demographic data for Pakistan to estimate the age of this founder mutation. RESULTS: We identified a small homozygous 0.694 Mb region around the KCNJ10 p.R65P mutation that had identical haplotypes in all of the patients which were completely absent in the control sample. Based on current demographic data and knowledge about disease frequency, we estimate that this particular p.R65P mutation arose 20 generations (about 500 years) ago. CONCLUSION: By knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling. |
format | Online Article Text |
id | pubmed-5023937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50239372016-09-20 Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome Abdelhadi, Ola Iancu, Daniela Tekman, Mehmet Stanescu, Horia Bockenhauer, Detlef Kleta, Robert Mol Genet Genomic Med Original Articles BACKGROUND: EAST syndrome is an autosomal recessive disorder caused by loss‐of‐function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to establish the existence of a potential founder effect in the Pakistani population. METHODS: To this end, we genotyped 12 patients from seven families and we compared disease haplotypes with ethnically matched control chromosomes. This haplotype was used together with demographic data for Pakistan to estimate the age of this founder mutation. RESULTS: We identified a small homozygous 0.694 Mb region around the KCNJ10 p.R65P mutation that had identical haplotypes in all of the patients which were completely absent in the control sample. Based on current demographic data and knowledge about disease frequency, we estimate that this particular p.R65P mutation arose 20 generations (about 500 years) ago. CONCLUSION: By knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling. John Wiley and Sons Inc. 2016-06-07 /pmc/articles/PMC5023937/ /pubmed/27652280 http://dx.doi.org/10.1002/mgg3.227 Text en © 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Abdelhadi, Ola Iancu, Daniela Tekman, Mehmet Stanescu, Horia Bockenhauer, Detlef Kleta, Robert Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome |
title | Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome |
title_full | Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome |
title_fullStr | Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome |
title_full_unstemmed | Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome |
title_short | Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome |
title_sort | founder mutation in kcnj10 in pakistani patients with east syndrome |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023937/ https://www.ncbi.nlm.nih.gov/pubmed/27652280 http://dx.doi.org/10.1002/mgg3.227 |
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