Journal article
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(6), pp.1452-1458
12/2003
DOI: 10.1086/380205
PMCID: PMC1180408
PMID: 14571368
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
GJB2
. 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.
Details
- Title: Subtitle
- Prevalence and Evolutionary Origins of the del(GJB6-D13S1830) Mutation in the DFNB1 Locus in Hearing-Impaired Subjects: a Multicenter Study
- Creators
- Ignacio del Castillo - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridMiguel A Moreno-Pelayo - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridFrancisco J del Castillo - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridZippora Brownstein - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridSandrine Marlin - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridQuint Adina - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridDavid J Cockburn - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridArti Pandya - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridKirby R Siemering - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridG. Parker Chamberlin - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridEster Ballana - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridWim Wuyts - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridAndréa Trevas Maciel-Guerra - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridAraceli Álvarez - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridManuela Villamar - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridMordechai Shohat - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridDvorah Abeliovich - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridHans-Henrik M Dahl - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridXavier Estivill - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridPaolo Gasparini - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridTim Hutchin - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridWalter E Nance - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridEdi L Sartorato - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridRichard J. H Smith - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridGuy Van Camp - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridKaren B Avraham - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridChristine Petit - Unidad de Genética Molecular, Hospital Ramón y Cajal, MadridFelipe Moreno - Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.73(6), pp.1452-1458
- DOI
- 10.1086/380205
- PMID
- 14571368
- PMCID
- PMC1180408
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- The American Society of Human Genetics
- Alternative title
- del(GJB6-D13S1830) Mutation in Deafness
- Language
- English
- Date published
- 12/2003
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006412202771
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