title: Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss.
abstract: Mutations in the Cx26 gene have been shown to cause autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB1 locus on chromosome 13q12. Using direct sequencing, we screened the Cx26 coding region of affected and nonaffected members from seven ARNSHL families either linked to the DFNB1 locus or in which the ARNSHL phenotype cosegregated with markers from chromosome 13q12. Cx26 mutations were found in six of the seven families and included two previously described mutations (W24X and W77X) and two novel Cx26 mutations: a single base pair deletion of nucleotide 35 resulting in a frameshift and a C-to-T substitution at nucleotide 370 resulting in a premature stop codon (Q124X). We have developed and optimized allele-specific PCR primers for each of the four mutations to rapidly determine carrier and noncarrier status within families. We also have developed a single stranded conformational polymorphism (SSCP) assay which covers the entire Cx26 coding region. This assay can be used to screen individuals with nonsyndromic hearing loss for mutations in the CX26 gene.
authors.affiliation: Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Scott
authors.forename: M L
authors.initials: ML
authors.lastname: Kraft
authors.forename: R
authors.initials: R
authors.lastname: Carmi
authors.forename: A
authors.initials: A
authors.lastname: Ramesh
authors.forename: K
authors.initials: K
authors.lastname: Elbedour
authors.forename: Y
authors.initials: Y
authors.lastname: Yairi
authors.forename: C R
authors.initials: CR
authors.lastname: Srisailapathy
authors.forename: S S
authors.initials: SS
authors.lastname: Rosengren
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
authors.forename: R F
authors.initials: RF
authors.lastname: Mueller
authors.forename: N J
authors.initials: NJ
authors.lastname: Lench
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002882:Chromosomes, Human, Pair 13; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006319:Hearing Loss, Sensorineural / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D015146:Midwestern United States / Q000453:epidemiology; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26