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 Estivill, Paolo GaspariniTim Hutchin, Walter E. Nance, Edi L. Sartorato, Richard J.H. Smith, Guy Van Camp, Karen B. Avraham, Christine Petit, Felipe Moreno*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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
Issue number6
StatePublished - Dec 2003


FundersFunder number
Consiglio Nazionale della Ricerche–Genomica Funzionale
European CommunityQLG2-CT-1999-00988
Flemish Fund for Scientific Research
Fondo de Investigaciones Sanitarias
Israel Ministry of Science, Culture and Sport
National Institutes of Health
National Institute on Deafness and Other Communication DisordersR01DC002842
Garnett Passe and Rodney Williams Memorial Foundation
Ministerio de Ciencia Tecnología y TelecomunicacionesFIS 00/0244, SAF99-0025, FIS PI020807
Comisión Interministerial de Ciencia y Tecnología


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