Faculty Collaboration Database

Connexin 26 and connexin 30 mutations in children with nonsyndromic hearing loss. Laryngoscope 2004 Apr;114(4):607-11

Date

04/06/2004

Pubmed ID

15064611

DOI

10.1097/00005537-200404000-00003

Scopus ID

2-s2.0-1842505708 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

OBJECTIVES/HYPOTHESIS: Mutations in the connexin 26 (Cx26) or gap junction beta 2 gene are the leading cause of hereditary nonsyndromic sensorineural hearing loss in Caucasians. The Cx26 coding region of 68 children with nonsyndromic sensorineural hearing loss was sequenced to determine the frequency and type of Cx26 mutations in this population. Screening was also performed for a common connexin 30 (Cx30) or gap junction beta 6 mutation (del [GJB6-D13S1830]). Children also underwent audiological testing to determine whether any correlation exists between Cx26 mutations and severity of hearing loss.

STUDY DESIGN: In all, 68 children with nonsyndromic sensorineural hearing loss were screened for Cx26 and Cx30 mutations by polymerase chain reaction and direct sequencing.

METHODS: Genomic DNA was amplified by polymerase chain reaction using primers that flank the entire Cx26 coding region. Screening for the 342-kb Cx30 deletion was performed using primers that amplified the breakpoint junction of the deletion. The amplicons were then sequenced in both directions and analyzed for mutations. Audiometric testing, including pure-tone audiometry and auditory evoked brainstem response, was also performed to determine the degree of hearing loss.

RESULTS: Twenty-seven of 68 children tested had mutations in Cx26 with 35delG being the most prevalent. Ten additional Cx26 mutations were detected including a novel compound heterozygote. Two children were heterozygous for the Cx30 del (GJB6-D13S1830) mutation.

CONCLUSION: Cx26 and Cx30 mutations were present in 41.2% of children tested in the study population. Audiometric data supported previous studies demonstrating a greater degree of hearing loss in subjects who are homozygous for the 35delG mutation.

Author List

Erbe CB, Harris KC, Runge-Samuelson CL, Flanary VA, Wackym PA

Authors

Valerie A. Flanary MD Director, Professor in the Otolaryngology department at Medical College of Wisconsin
Christina Runge PhD Associate Provost, Chief, Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Audiometry, Pure-Tone
Child
Child, Preschool
Connexin 26
Connexin 30
Connexins
DNA Mutational Analysis
DNA Primers
Female
Gene Deletion
Gene Expression
Hearing Loss, Sensorineural
Humans
Infant
Male
Mass Screening
Point Mutation
Polymerase Chain Reaction
Severity of Illness Index