Prevalence and Evolutionary Origins of the del(GJB6-D13S1830) Mutation in the DFNB1 Locus in Hearing-Impaired Subjects

A Multicenter Study

Ignacio Del Castillo, Miguel A. Moreno-Pelayo, Francisco J. Del Castillo, Zippora Brownstein, Sandrine Marlin, Quint Adina, David J. Cockburn, Arti Pandya, Kirby R. Siemering, G. Parker Chamberlin, Ester Ballana, Wim Wuyts, Andréa Trevas Maciel-Guerra, Araceli Álvarez, Manuela Villamar, Mordechai Shohat, Dvorah Abeliovich, Hans Henrik M Dahl, Xavier P. Estivill, Paolo Gasparini & 8 others Tim Hutchin, Walter E. Nance, Edi L. Sartorato, Richard J H Smith, Guy Van Camp, Karen B. Avraham, Christine Petit, Felipe Moreno

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

Mutations in GJB2, the gene encoding connexin-26 at the DFNB1 locus on 13q12, are found in as many as 50% of subjects with autosomal recessive, nonsyndromic prelingual hearing impairment. However, genetic diagnosis is complicated by the fact that 10%-50% of affected subjects with GJB2 mutations carry only one mutant allele. Recently, a deletion truncating the GJB6 gene (encoding connexin-30), near GJB2 on 13q12, was shown to be the accompanying mutation in ∼50% of these deaf GJB2 heterozygotes in a cohort of Spanish patients, thus becoming second only to 35delG at GJB2 as the most frequent mutation causing prelingual hearing impairment in Spain. Here, we present data from a multicenter study in nine countries that shows that the deletion is present in most of the screened populations, with higher frequencies in France, Spain, and Israel, where the percentages of unexplained GJB2 heterozygotes fell to 16.0%-20.9% after screening for the del(GJB6-D13S1830) mutation. Our results also suggest that additional mutations remain to be identified, either in DFNB1 or in other unlinked genes involved in epistatic interactions with G/B2. Analysis of haplotypes associated with the deletion revealed a founder effect in Ashkenazi Jews and also suggested a common founder for countries in Western Europe. These results have important implications for the diagnosis and counseling of families with DFNB1 deafness.

Original languageEnglish
Pages (from-to)1452-1458
Number of pages7
JournalAmerican Journal of Human Genetics
Volume73
Issue number6
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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Hearing
Multicenter Studies
Mutation
Heterozygote
Spain
Genes
Founder Effect
Jews
Connexins
Deafness
Israel
Hearing Loss
Haplotypes
France
Counseling
Alleles
Population

ASJC Scopus subject areas

  • Genetics

Cite this

Del Castillo, I., Moreno-Pelayo, M. A., Del Castillo, F. J., Brownstein, Z., Marlin, S., Adina, Q., ... Moreno, F. (2003). Prevalence and Evolutionary Origins of the del(GJB6-D13S1830) Mutation in the DFNB1 Locus in Hearing-Impaired Subjects: A Multicenter Study. American Journal of Human Genetics, 73(6), 1452-1458. https://doi.org/10.1086/380205

Prevalence and Evolutionary Origins of the del(GJB6-D13S1830) Mutation in the DFNB1 Locus in Hearing-Impaired Subjects : A Multicenter Study. / Del Castillo, Ignacio; Moreno-Pelayo, Miguel A.; Del Castillo, Francisco J.; Brownstein, Zippora; Marlin, Sandrine; Adina, Quint; Cockburn, David J.; Pandya, Arti; Siemering, Kirby R.; Chamberlin, G. Parker; Ballana, Ester; Wuyts, Wim; Maciel-Guerra, Andréa Trevas; Álvarez, Araceli; Villamar, Manuela; Shohat, Mordechai; Abeliovich, Dvorah; Dahl, Hans Henrik M; Estivill, Xavier P.; Gasparini, Paolo; Hutchin, Tim; Nance, Walter E.; Sartorato, Edi L.; Smith, Richard J H; Van Camp, Guy; Avraham, Karen B.; Petit, Christine; Moreno, Felipe.

In: American Journal of Human Genetics, Vol. 73, No. 6, 12.2003, p. 1452-1458.

Research output: Contribution to journalArticle

Del Castillo, I, Moreno-Pelayo, MA, Del Castillo, FJ, Brownstein, Z, Marlin, S, Adina, Q, Cockburn, DJ, Pandya, A, Siemering, KR, Chamberlin, GP, Ballana, E, Wuyts, W, Maciel-Guerra, AT, Álvarez, A, Villamar, M, Shohat, M, Abeliovich, D, Dahl, HHM, Estivill, XP, Gasparini, P, Hutchin, T, Nance, WE, Sartorato, EL, Smith, RJH, Van Camp, G, Avraham, KB, Petit, C & Moreno, F 2003, 'Prevalence and Evolutionary Origins of the del(GJB6-D13S1830) Mutation in the DFNB1 Locus in Hearing-Impaired Subjects: A Multicenter Study', American Journal of Human Genetics, vol. 73, no. 6, pp. 1452-1458. https://doi.org/10.1086/380205
Del Castillo, Ignacio ; Moreno-Pelayo, Miguel A. ; Del Castillo, Francisco J. ; Brownstein, Zippora ; Marlin, Sandrine ; Adina, Quint ; Cockburn, David J. ; Pandya, Arti ; Siemering, Kirby R. ; Chamberlin, G. Parker ; Ballana, Ester ; Wuyts, Wim ; Maciel-Guerra, Andréa Trevas ; Álvarez, Araceli ; Villamar, Manuela ; Shohat, Mordechai ; Abeliovich, Dvorah ; Dahl, Hans Henrik M ; Estivill, Xavier P. ; Gasparini, Paolo ; Hutchin, Tim ; Nance, Walter E. ; Sartorato, Edi L. ; Smith, Richard J H ; Van Camp, Guy ; Avraham, Karen B. ; Petit, Christine ; Moreno, Felipe. / Prevalence and Evolutionary Origins of the del(GJB6-D13S1830) Mutation in the DFNB1 Locus in Hearing-Impaired Subjects : A Multicenter Study. In: American Journal of Human Genetics. 2003 ; Vol. 73, No. 6. pp. 1452-1458.
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abstract = "Mutations in GJB2, the gene encoding connexin-26 at the DFNB1 locus on 13q12, are found in as many as 50{\%} of subjects with autosomal recessive, nonsyndromic prelingual hearing impairment. However, genetic diagnosis is complicated by the fact that 10{\%}-50{\%} of affected subjects with GJB2 mutations carry only one mutant allele. Recently, a deletion truncating the GJB6 gene (encoding connexin-30), near GJB2 on 13q12, was shown to be the accompanying mutation in ∼50{\%} of these deaf GJB2 heterozygotes in a cohort of Spanish patients, thus becoming second only to 35delG at GJB2 as the most frequent mutation causing prelingual hearing impairment in Spain. Here, we present data from a multicenter study in nine countries that shows that the deletion is present in most of the screened populations, with higher frequencies in France, Spain, and Israel, where the percentages of unexplained GJB2 heterozygotes fell to 16.0{\%}-20.9{\%} after screening for the del(GJB6-D13S1830) mutation. Our results also suggest that additional mutations remain to be identified, either in DFNB1 or in other unlinked genes involved in epistatic interactions with G/B2. Analysis of haplotypes associated with the deletion revealed a founder effect in Ashkenazi Jews and also suggested a common founder for countries in Western Europe. These results have important implications for the diagnosis and counseling of families with DFNB1 deafness.",
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AU - Del Castillo, Ignacio

AU - Moreno-Pelayo, Miguel A.

AU - Del Castillo, Francisco J.

AU - Brownstein, Zippora

AU - Marlin, Sandrine

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AU - Cockburn, David J.

AU - Pandya, Arti

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AU - Chamberlin, G. Parker

AU - Ballana, Ester

AU - Wuyts, Wim

AU - Maciel-Guerra, Andréa Trevas

AU - Álvarez, Araceli

AU - Villamar, Manuela

AU - Shohat, Mordechai

AU - Abeliovich, Dvorah

AU - Dahl, Hans Henrik M

AU - Estivill, Xavier P.

AU - Gasparini, Paolo

AU - Hutchin, Tim

AU - Nance, Walter E.

AU - Sartorato, Edi L.

AU - Smith, Richard J H

AU - Van Camp, Guy

AU - Avraham, Karen B.

AU - Petit, Christine

AU - Moreno, Felipe

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