SPECTRUM AND FREQUENCIES OF MUTATIONS IN GJB2 AND GJB6 AMONG ARGENTINEAN PATIENTS WITH SENSORINEURAL NON-SYNDROMIC DEAFNESS.

DALAMON V; WERNERT F; ANA BELEN ELGOYHEN

Hinxton

Congreso; The 8th Molecular Biology of Hearing & Deafness Confrence; 2011

Welcome Trust Conference Center, Sanger Institute

Genetically caused congenital deafness is a common trait affecting 1 in 2000 children. Most cases are non-syndromic and of autosomal recessive inheritance. To date, over 40 different genes have been identified as genetic cause of deafness worldwide. The aim of this study was to investigate and report the spectrum and frequency of mutations in GJB2, GJB6, OTOF and MT-RNR1, in deaf patients from Argentina. A total of 773 samples were analyzed; 447 from non-syndromic unrelated Argentinean deaf patients (99 familial and 348 sporadic cases) and 326 from relatives and siblings. Most of them were of prelingual onset (83%). At the time of the study 78 patients were already cochlear implanted. Mutations in GJB2 and GJB6 genes were found in 156 patients, accounting for 35% of the sample. Overall 40 different sequence variations were identified. The mutation c.35delG accounted for 55/447 (12%) of the patients studied, resulting in 35% of the detected mutations, becoming the most frequent causing mutation in our population, in accordance with other reports worldwide. Only 2% of patients showed mutations in the GJB6 gene (seven del(GJB6-D13S1830) and three del(GJB6-D13S1854)), resultaing in 6% of the detected mutations. Overall sequence variations identified in GJB2 gene were: T8M, T8T, L10P, G12V, c.35delG, S19T, V27I, M34T, V37I, E47X, c.167delT, R75W, R75Q, W77R, c.233insG, A78S, I82M, F83L, V84L, L90P, c.269insT, V95M, c.312del14nt, G109V, c.333delAA, R127H, I128I, E129K, R143W, V153I, G160S, M163V, M163L, K168R, R184P, V190D, c.682 C>T (3´UTR), IVS1+1G>A.  Three of them are reported for the first time in GJB2 gene: c.233 insG, p.V190D and p.A78S. Neither mutation Q829X in OTOF nor m.A1555G in MT-RNR1 were found in our cohort. Nevertheless variation m.A827G in MT-RNR1 was detected in two patients. The present study demonstrates that different mutations in the GJB2 and GJB6 genes are prevalent in our Argentinean population, most importantly, it adds three novel GJB2 mutations to be taken in consideration in the genetic diagnosis of sensorineural non-syndromic hearing loss.  These findings strengthen the importance of genetic screening in hearing-impaired patients for the contribution towards an adequate genetic counseling and treatment planning.