Mutation analysis of the Cx26, Cx30, and Cx31 genes in autosomal recessive nonsyndromic hearing impairment.
CONCLUSIONS
Biallelic Cx26 mutations are the most common cause of autosomal recessive nonsyndromic hearing impairment (ARNHI) in Switzerland. Mutations in Cx30 and 31, digenic mutations as well as large deletions/duplications, are unlikely to be a major cause of hearing loss in Swiss patients with ARNHI. Multiplex ligation-dependent probe amplification (MLPA) is a highly accurate screening method for detection of c.del(GJB6-D13S1830).


OBJECTIVE
The intent of this study was to investigate the prevalence of the point and digenic mutations including large deletions and duplications in the Cx26, 30, and 31 genes in a Swiss patient cohort with ARNHI and cochlear implant.


METHODS
The coding regions of Cx26, 30, and 31 were sequenced in 32 patients. Large deletions/duplications were assessed by MLPA.


RESULTS
In one patient digenic heterozygous mutations involving Cx26 (c.35delG) and Cx30 (c.del(GJB6-D13S1830)) were identified. Biallelic Cx26 mutations were detected in 31%. One putative mutation (c.94C>T) was found in Cx31. MLPA analysis did not reveal any additional deletion or duplication in all three Cx genes, except for the heterozygous c.del(GJB6-D13S1830) deletion.
Gürtler
Nicolas
N
Hals-Nasen-Ohren-Klinik, Kantonsspital, Aarau, Switzerland. nicolas.guertler@ksa.ch
Egenter
Carole
C
Bösch
Nemya
N
Plasilova
Martina
M
D016022:Case-Control Studies; D003054:Cochlear Implants; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics* / Q000601:surgery; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26