title: Phenotypic variability of non-syndromic hearing loss in patients heterozygous for both c.35delG of GJB2 and the 342-kb deletion involving GJB6.
abstract: Mutations in GJB2, encoding the gap junction protein connexin 26, are the most common cause of inherited non-syndromic hearing loss (NSHL), with a broad spectrum of mutations leading to recessive as well as dominant forms. It has been shown that patients who are compound heterozygous for a 342-kb deletion (Delta(GJB6-D13S1830)) involving a large portion of the 5'-part of GJB6, encoding connexin 30, and a GJB2 mutation develop NSHL due to a trait with a digenic pattern of inheritance. We have used a mutation-specific polymerase chain reaction assay to screen NSHL patients for the presence of Delta(GJB6-D13S1830) and identified two families segregating both c.35delG in GJB2 and Delta(GJB6-D13S1830). Remarkably, the severity of hearing loss due to heterozygosity for c.35delG in GJB2 in conjunction with Delta(GJB6-D13S1830) is considerably different in members of the two families, ranging from congenital deafness in one to moderate/severe hearing loss with congenital onset in the other case.
authors.affiliation: Institute of Human Genetics, University Hospital Hamburg-Eppendorf, Hamburg, Germany. bolz@uke.uni-hamburg.de
authors.forename: Hanno
authors.initials: H
authors.lastname: Bolz
authors.forename: Götz
authors.initials: G
authors.lastname: Schade
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ehmer
authors.forename: Christian
authors.initials: C
authors.lastname: Kothe
authors.forename: Markus
authors.initials: M
authors.lastname: Hess
authors.forename: Andreas
authors.initials: A
authors.lastname: Gal
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D017629:Gap Junctions / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26