Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype–phenotype analysis in moderate cases
- 397 Downloads
This paper presents a mutation as well as a genotype–phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort.
KeywordsGJB2 Connexin 26 GJB6 Deafness Novel mutations Hearing loss Molecular study Autosomal recessive deafness DFNB1 Moderate hearing loss
We would like to thank all families that participated in this study. This study was supported by an International Research Scholar grant from the Howard Hughes Medical Institute and the Tinnitus Research Initiative to Ana Belen Elgoyhen and by ANPCyT, Argentina, to Viviana Dalamon. María Florencia Wernert is a CONICET fellow.
Conflict of interest
The authors declare no conflicts of interest.
- 5.Scott DA, Carmi R, Kraft ML, Ramesh A, Elbedour K, Yairi Y, Srisailapathy CR, Rosengren SS, Markham AF, Mueller RF, Lench NJ, Van Camp G, Smith RJ, Sheffield VC (1998) Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss. Hum Mutat 11(5):387–394PubMedCrossRefGoogle Scholar
- 19.Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14(1): 33-8–27-8Google Scholar
- 20.Hilgert N et al. (2009) Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene. Eur J Hum Genet 17:517–524Google Scholar
- 25.Esmaeili M, Bonyadi M, Nejadkazem M (2007) Common mutation analysis of GJB2 and GJB6 genes in affected families with autosomal recessive non-syndromic hearing loss from Iran: simultaneous detection of two common mutations (35delG/del(GJB6-D13S1830)) in the DFNB1-related deafness. Int J Pediatr Otorhinolaryngol 71(6):869–873PubMedCrossRefGoogle Scholar
- 33.Li L, Lu J, Tao Z, Huang Q, Chai Y et al (2012) The p.V37I exclusive genotype of GJB2: a genetic risk-indicator of postnatal permanent childhood hearing impairment. PLoS One 7(5): e36621Google Scholar
- 35.Sinnathuray AR et al (2004) Connexin 26 (GJB2) gene-related deafness and speech intelligibility after cochlear implantation Auditory perception and speech discrimination after cochlear implantation in patients with connexin 26 (GJB2) gene-related deafness. Otol Neurotol 25(6):935–942PubMedCrossRefGoogle Scholar