Connexin 26 and connexin 30 mutations in children with nonsyndromic hearing loss.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Erbe
Christy B
CB
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.
Harris
Kevin C
KC
Runge-Samuelson
Christina L
CL
Flanary
Valerie A
VA
Wackym
Phillip Ashley
PA
D000293:Adolescent; D001301:Audiometry, Pure-Tone / Q000379:methods; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D008403:Mass Screening / Q000379:methods; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index
D000075302:Connexin 30; D017630:Connexins; D017931:DNA Primers; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26