Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Abdelhadi, Ola, Iancu, Daniela, Tekman, Mehmet, Stanescu, Horia, Bockenhauer, Detlef, Kleta, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
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
_version_ 1782453714770984960
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
work_keys_str_mv AT abdelhadiola foundermutationinkcnj10inpakistanipatientswitheastsyndrome
AT iancudaniela foundermutationinkcnj10inpakistanipatientswitheastsyndrome
AT tekmanmehmet foundermutationinkcnj10inpakistanipatientswitheastsyndrome
AT stanescuhoria foundermutationinkcnj10inpakistanipatientswitheastsyndrome
AT bockenhauerdetlef foundermutationinkcnj10inpakistanipatientswitheastsyndrome
AT kletarobert foundermutationinkcnj10inpakistanipatientswitheastsyndrome