Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey

Duygu Duman, Asli Sirmaci, F. Basak Cengiz, Hilal Ozdag, Mustafa Tekin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

More than 60% of prelingual deafness is genetic in origin, and of these up to 95% are monogenic autosomal recessive traits. Causal mutations have been identified in 1 of 38 different genes in a subset of patients with nonsyndromic autosomal recessive deafness. In this study, we screened 49 unrelated Turkish families with at least three affected children born to consanguineous parents. Probands from all families were negative for mutations in the GJB2 gene, two large deletions in the GJB6 gene, and the 1555A>G substitution in the mitochondrial DNA MTRNR1 gene. Each family was subsequently screened via autozygosity mapping with genomewide single-nucleotide polymorphism arrays. If the phenotype cosegregated with a haplotype flanking one of the 38 genes, mutation analysis of the gene was performed. We identified 22 different autozygous mutations in 11 genes, other than GJB2, in 26 of 49 families, which overall explains deafness in 62% of families. Relative frequencies of genes following GJB2 were MYO15A (9.9%), TMIE (6.6%), TMC1 (6.6%), OTOF (5.0%), CDH23 (3.3%), MYO7A (3.3%), SLC26A4 (1.7%), PCDH15 (1.7%), LRTOMT (1.7%), SERPINB6 (1.7%), and TMPRSS3 (1.7%). Nineteen of 22 mutations are reported for the first time in this study. Unknown rare genes for deafness appear to be present in the remaining 23 families.

Original languageEnglish
Pages (from-to)29-33
Number of pages5
JournalGenetic Testing and Molecular Biomarkers
Volume15
Issue number1-2
DOIs
StatePublished - Jan 1 2011

Fingerprint

Turkey
Mutation
Genes
Deafness
Nonsyndromic Deafness
Mitochondrial DNA
Gene Frequency
Haplotypes
Single Nucleotide Polymorphism
Parents
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey. / Duman, Duygu; Sirmaci, Asli; Cengiz, F. Basak; Ozdag, Hilal; Tekin, Mustafa.

In: Genetic Testing and Molecular Biomarkers, Vol. 15, No. 1-2, 01.01.2011, p. 29-33.

Research output: Contribution to journalArticle

Duman, Duygu ; Sirmaci, Asli ; Cengiz, F. Basak ; Ozdag, Hilal ; Tekin, Mustafa. / Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey. In: Genetic Testing and Molecular Biomarkers. 2011 ; Vol. 15, No. 1-2. pp. 29-33.
@article{d2db27b47c1249f3be183a23f65deafa,
title = "Screening of 38 genes identifies mutations in 62{\%} of families with nonsyndromic deafness in Turkey",
abstract = "More than 60{\%} of prelingual deafness is genetic in origin, and of these up to 95{\%} are monogenic autosomal recessive traits. Causal mutations have been identified in 1 of 38 different genes in a subset of patients with nonsyndromic autosomal recessive deafness. In this study, we screened 49 unrelated Turkish families with at least three affected children born to consanguineous parents. Probands from all families were negative for mutations in the GJB2 gene, two large deletions in the GJB6 gene, and the 1555A>G substitution in the mitochondrial DNA MTRNR1 gene. Each family was subsequently screened via autozygosity mapping with genomewide single-nucleotide polymorphism arrays. If the phenotype cosegregated with a haplotype flanking one of the 38 genes, mutation analysis of the gene was performed. We identified 22 different autozygous mutations in 11 genes, other than GJB2, in 26 of 49 families, which overall explains deafness in 62{\%} of families. Relative frequencies of genes following GJB2 were MYO15A (9.9{\%}), TMIE (6.6{\%}), TMC1 (6.6{\%}), OTOF (5.0{\%}), CDH23 (3.3{\%}), MYO7A (3.3{\%}), SLC26A4 (1.7{\%}), PCDH15 (1.7{\%}), LRTOMT (1.7{\%}), SERPINB6 (1.7{\%}), and TMPRSS3 (1.7{\%}). Nineteen of 22 mutations are reported for the first time in this study. Unknown rare genes for deafness appear to be present in the remaining 23 families.",
author = "Duygu Duman and Asli Sirmaci and Cengiz, {F. Basak} and Hilal Ozdag and Mustafa Tekin",
year = "2011",
month = "1",
day = "1",
doi = "10.1089/gtmb.2010.0120",
language = "English",
volume = "15",
pages = "29--33",
journal = "Genetic Testing and Molecular Biomarkers",
issn = "1945-0265",
publisher = "Mary Ann Liebert Inc.",
number = "1-2",

}

TY - JOUR

T1 - Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey

AU - Duman, Duygu

AU - Sirmaci, Asli

AU - Cengiz, F. Basak

AU - Ozdag, Hilal

AU - Tekin, Mustafa

PY - 2011/1/1

Y1 - 2011/1/1

N2 - More than 60% of prelingual deafness is genetic in origin, and of these up to 95% are monogenic autosomal recessive traits. Causal mutations have been identified in 1 of 38 different genes in a subset of patients with nonsyndromic autosomal recessive deafness. In this study, we screened 49 unrelated Turkish families with at least three affected children born to consanguineous parents. Probands from all families were negative for mutations in the GJB2 gene, two large deletions in the GJB6 gene, and the 1555A>G substitution in the mitochondrial DNA MTRNR1 gene. Each family was subsequently screened via autozygosity mapping with genomewide single-nucleotide polymorphism arrays. If the phenotype cosegregated with a haplotype flanking one of the 38 genes, mutation analysis of the gene was performed. We identified 22 different autozygous mutations in 11 genes, other than GJB2, in 26 of 49 families, which overall explains deafness in 62% of families. Relative frequencies of genes following GJB2 were MYO15A (9.9%), TMIE (6.6%), TMC1 (6.6%), OTOF (5.0%), CDH23 (3.3%), MYO7A (3.3%), SLC26A4 (1.7%), PCDH15 (1.7%), LRTOMT (1.7%), SERPINB6 (1.7%), and TMPRSS3 (1.7%). Nineteen of 22 mutations are reported for the first time in this study. Unknown rare genes for deafness appear to be present in the remaining 23 families.

AB - More than 60% of prelingual deafness is genetic in origin, and of these up to 95% are monogenic autosomal recessive traits. Causal mutations have been identified in 1 of 38 different genes in a subset of patients with nonsyndromic autosomal recessive deafness. In this study, we screened 49 unrelated Turkish families with at least three affected children born to consanguineous parents. Probands from all families were negative for mutations in the GJB2 gene, two large deletions in the GJB6 gene, and the 1555A>G substitution in the mitochondrial DNA MTRNR1 gene. Each family was subsequently screened via autozygosity mapping with genomewide single-nucleotide polymorphism arrays. If the phenotype cosegregated with a haplotype flanking one of the 38 genes, mutation analysis of the gene was performed. We identified 22 different autozygous mutations in 11 genes, other than GJB2, in 26 of 49 families, which overall explains deafness in 62% of families. Relative frequencies of genes following GJB2 were MYO15A (9.9%), TMIE (6.6%), TMC1 (6.6%), OTOF (5.0%), CDH23 (3.3%), MYO7A (3.3%), SLC26A4 (1.7%), PCDH15 (1.7%), LRTOMT (1.7%), SERPINB6 (1.7%), and TMPRSS3 (1.7%). Nineteen of 22 mutations are reported for the first time in this study. Unknown rare genes for deafness appear to be present in the remaining 23 families.

UR - http://www.scopus.com/inward/record.url?scp=79951991591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951991591&partnerID=8YFLogxK

U2 - 10.1089/gtmb.2010.0120

DO - 10.1089/gtmb.2010.0120

M3 - Article

C2 - 21117948

AN - SCOPUS:79951991591

VL - 15

SP - 29

EP - 33

JO - Genetic Testing and Molecular Biomarkers

JF - Genetic Testing and Molecular Biomarkers

SN - 1945-0265

IS - 1-2

ER -