Spectrum and frequencies of mutations in GJB2 and GJB6 among Argentinean patients with sensorineural non-syndromic deafness.

DALAMÓN V; ELGOYHEN AB

Baltimore USA

Congreso; 34th Midwinter Meeting, Association for Research in Otolaryngology; 2011

Spectrum and frequencies of mutations in GJB2 and GJB6 among Argentinean patients with sensorineural non-syndromic deafness. Genetically caused congenital deafness is a common trait affecting 1 in 2000 children. Most cases are non-syndromic and autosomal recessive inheritance accounts for about 70-80%. To date, over 40 different genes have been identified, but mutations in the GJB2 gene, encoding connexin 26, is one of the most common genetic causes 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; 439 from non-syndromic unrelated Argentinean deaf patients (99 familial and 340 sporadic cases) derived from different Otorhinolaryngology or Genetic Services and 334 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 36% of the sample. Overall 38 different sequence variations were identified. The mutation c.35delG accounted for 55/439 (13%) 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)). In addition, 35 sequence variations different from c.35delG, were identified in the GJB2 gene: T8M, L10P, G12V, S19T, V27I, M34T, V37I, E47X, 167delT, R75W, R75Q, c.233 insG, W77R, 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. Four of them are reported for the first time (las nombraria entre paréntesis) .None of the samples showed mutations either in OTOF or in MT-RNR1. The present study demonstrates that different mutations in the GJB2 and GJB6 genes are prevalent in our Argentinean population. These findings strengthen the importance of genetic screening in hearing-impaired patients for the contribution towards an adequate genetic counseling and treatment planning.