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A Novel Connexin 26 Compound Heterozygous Mutation Results in Deafness
Author(s) -
Harris Kevin C.,
Erbe Christy B.,
Firszt Jill B.,
Flanary Valerie A.,
Wackym Phillip A.
Publication year - 2002
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200207000-00003
Subject(s) - compound heterozygosity , heterozygote advantage , genetics , hearing loss , mutation , biology , connexin , allele , gene , medicine , audiology , intracellular , gap junction
Objective Mutations of the gap junction beta 2 (GJB2) gene coding for the protein connexin 26 account for up to 50% of nonsyndromic sensorineural hearing loss (NSHL), with specific mutations associated with distinct ethnic groups. A biracial family with nonsyndromic sensorineural deafness consistent with autosomal recessive inheritance was examined for connexin 26 (Cx26) mutations. Study Design Prospective observational study. Methods A family consisting of a Caucasian mother and a Chinese father with two of six children affected by NSHL was examined for Cx26 mutations. Peripheral blood lymphocyte DNA was used to amplify by polymerase chain reaction the Cx26 coding region, followed by mutation detection enhancement gel screening and complete sequencing. Phenotypic characterization using audiometric testing was completed for all children and both parents. Results The two affected children were found to be compound heterozygotes for Cx26 mutations, displaying a previously unreported combination of 35delG and 235delC. The parents were each unaffected heterozygotes consistent with their ethnic heritage, specifically, the Caucasian mother a 35delG heterozygote and the Chinese father a 235delC heterozygote. Conclusions Connexin 26 mutations account for a significant proportion of NSHL worldwide, with specific mutations linked to distinct ethnic groups. Genetic analysis of a biracial family with NSHL revealed a novel 35delG/235delC compound heterozygous state in phenotypically affected children. These results highlight the usefulness of Cx26 mutation screening for genetic counseling and suggest that the 235delC mutation is present in China as it is in Japan and Korea.