Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Guney Bademci, Joseph Foster, Nejat Mahdieh, Mortaza Bonyadi, Duygu Duman, F. Basak Cengiz, Ibis Menendez, Oscar Diaz-Horta, Atefeh Shirkavand, Sirous Zeinali, Asli Subasioglu, Suna Tokgoz-Yilmaz, Fabiola Huesca-Hernandez, Maria De La Luz Arenas-Sordo, Juan Dominguez-Aburto, Edgar Hernandez-Zamora, Paola Montenegro, Rosario Paredes, Germania Moreta, Rodrigo VinuezaFranklin Villegas, Santiago Mendoza-Benitez, Shengru Guo, Nazim Bozan, Tulay Tos, Armagan Incesulu, Gonca Sennaroglu, Susan H Blanton, Hatice Ozturkmen-Akay, Muzeyyen Yildirim-Baylan, Mustafa Tekin

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

Original languageEnglish (US)
Pages (from-to)364-371
Number of pages8
JournalGenetics in Medicine
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Exome
Mutation
Genes
Founder Effect
Ecuador
Viverridae
Puerto Rico
Genetic Heterogeneity
Autosomal Recessive Deafness
Nonsyndromic Deafness
Deafness
Iran
Turkey
Mexico
Haplotypes
DNA

Keywords

  • autosomal recessive
  • deafness
  • exome
  • next-generation sequencing

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort. / Bademci, Guney; Foster, Joseph; Mahdieh, Nejat; Bonyadi, Mortaza; Duman, Duygu; Cengiz, F. Basak; Menendez, Ibis; Diaz-Horta, Oscar; Shirkavand, Atefeh; Zeinali, Sirous; Subasioglu, Asli; Tokgoz-Yilmaz, Suna; Huesca-Hernandez, Fabiola; De La Luz Arenas-Sordo, Maria; Dominguez-Aburto, Juan; Hernandez-Zamora, Edgar; Montenegro, Paola; Paredes, Rosario; Moreta, Germania; Vinueza, Rodrigo; Villegas, Franklin; Mendoza-Benitez, Santiago; Guo, Shengru; Bozan, Nazim; Tos, Tulay; Incesulu, Armagan; Sennaroglu, Gonca; Blanton, Susan H; Ozturkmen-Akay, Hatice; Yildirim-Baylan, Muzeyyen; Tekin, Mustafa.

In: Genetics in Medicine, Vol. 18, No. 4, 01.04.2016, p. 364-371.

Research output: Contribution to journalArticle

Bademci, G, Foster, J, Mahdieh, N, Bonyadi, M, Duman, D, Cengiz, FB, Menendez, I, Diaz-Horta, O, Shirkavand, A, Zeinali, S, Subasioglu, A, Tokgoz-Yilmaz, S, Huesca-Hernandez, F, De La Luz Arenas-Sordo, M, Dominguez-Aburto, J, Hernandez-Zamora, E, Montenegro, P, Paredes, R, Moreta, G, Vinueza, R, Villegas, F, Mendoza-Benitez, S, Guo, S, Bozan, N, Tos, T, Incesulu, A, Sennaroglu, G, Blanton, SH, Ozturkmen-Akay, H, Yildirim-Baylan, M & Tekin, M 2016, 'Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort', Genetics in Medicine, vol. 18, no. 4, pp. 364-371. https://doi.org/10.1038/gim.2015.89
Bademci, Guney ; Foster, Joseph ; Mahdieh, Nejat ; Bonyadi, Mortaza ; Duman, Duygu ; Cengiz, F. Basak ; Menendez, Ibis ; Diaz-Horta, Oscar ; Shirkavand, Atefeh ; Zeinali, Sirous ; Subasioglu, Asli ; Tokgoz-Yilmaz, Suna ; Huesca-Hernandez, Fabiola ; De La Luz Arenas-Sordo, Maria ; Dominguez-Aburto, Juan ; Hernandez-Zamora, Edgar ; Montenegro, Paola ; Paredes, Rosario ; Moreta, Germania ; Vinueza, Rodrigo ; Villegas, Franklin ; Mendoza-Benitez, Santiago ; Guo, Shengru ; Bozan, Nazim ; Tos, Tulay ; Incesulu, Armagan ; Sennaroglu, Gonca ; Blanton, Susan H ; Ozturkmen-Akay, Hatice ; Yildirim-Baylan, Muzeyyen ; Tekin, Mustafa. / Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort. In: Genetics in Medicine. 2016 ; Vol. 18, No. 4. pp. 364-371.
@article{40fd63292856402786cd6ab521f19244,
title = "Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort",
abstract = "Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56{\%}) families, 54{\%} of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13{\%}), MYO7A (11{\%}), SLC26A4 (10{\%}), TMPRSS3 (9{\%}), TMC1 (8{\%}), ILDR1 (6{\%}), and CDH23 (4{\%}). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56{\%} of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.",
keywords = "autosomal recessive, deafness, exome, next-generation sequencing",
author = "Guney Bademci and Joseph Foster and Nejat Mahdieh and Mortaza Bonyadi and Duygu Duman and Cengiz, {F. Basak} and Ibis Menendez and Oscar Diaz-Horta and Atefeh Shirkavand and Sirous Zeinali and Asli Subasioglu and Suna Tokgoz-Yilmaz and Fabiola Huesca-Hernandez and {De La Luz Arenas-Sordo}, Maria and Juan Dominguez-Aburto and Edgar Hernandez-Zamora and Paola Montenegro and Rosario Paredes and Germania Moreta and Rodrigo Vinueza and Franklin Villegas and Santiago Mendoza-Benitez and Shengru Guo and Nazim Bozan and Tulay Tos and Armagan Incesulu and Gonca Sennaroglu and Blanton, {Susan H} and Hatice Ozturkmen-Akay and Muzeyyen Yildirim-Baylan and Mustafa Tekin",
year = "2016",
month = "4",
day = "1",
doi = "10.1038/gim.2015.89",
language = "English (US)",
volume = "18",
pages = "364--371",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

AU - Bademci, Guney

AU - Foster, Joseph

AU - Mahdieh, Nejat

AU - Bonyadi, Mortaza

AU - Duman, Duygu

AU - Cengiz, F. Basak

AU - Menendez, Ibis

AU - Diaz-Horta, Oscar

AU - Shirkavand, Atefeh

AU - Zeinali, Sirous

AU - Subasioglu, Asli

AU - Tokgoz-Yilmaz, Suna

AU - Huesca-Hernandez, Fabiola

AU - De La Luz Arenas-Sordo, Maria

AU - Dominguez-Aburto, Juan

AU - Hernandez-Zamora, Edgar

AU - Montenegro, Paola

AU - Paredes, Rosario

AU - Moreta, Germania

AU - Vinueza, Rodrigo

AU - Villegas, Franklin

AU - Mendoza-Benitez, Santiago

AU - Guo, Shengru

AU - Bozan, Nazim

AU - Tos, Tulay

AU - Incesulu, Armagan

AU - Sennaroglu, Gonca

AU - Blanton, Susan H

AU - Ozturkmen-Akay, Hatice

AU - Yildirim-Baylan, Muzeyyen

AU - Tekin, Mustafa

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

AB - Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

KW - autosomal recessive

KW - deafness

KW - exome

KW - next-generation sequencing

UR - http://www.scopus.com/inward/record.url?scp=84962614845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962614845&partnerID=8YFLogxK

U2 - 10.1038/gim.2015.89

DO - 10.1038/gim.2015.89

M3 - Article

C2 - 26226137

AN - SCOPUS:84962614845

VL - 18

SP - 364

EP - 371

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 4

ER -