Carrier frequency of GJB2 and GJB6 variants in the Argentinean population with sensorineural non-syndromic deafness

DALAMÓN V; ELGOYHEN AB

Berlin- Alemania

Congreso; Congreso.Collegium Oto-Rhino-Laryngologicum Amictiae Sacrum.; 2008

Background: Approximately 1/1000 children are born with hearing impairment, half due to genetic causes. Autosomal recessive non-syndromic sensorineural hearing impairment (ARNSHI) comprises 80% of cases. Mutations in the GJB2 gene, encoding connexin 26, are the major cause in the Caucasian population. Study design: The aim of this study was to report the spectrum and frequency of mutations in GJB2 and GJB6 in deaf patients from Argentina. A total of 434 samples were analyzed; 252 from non-syndromic unrelated patients diagnosed with sensorineural hearing loss (167 cochlear implanted), and 182 from relatives and siblings. Results: Mutations in GJB2 and GJB6 were found in 86 patients (34%) showing 34 different genotypes: biallelic mutations were detected in 37 of them (43%), only one mutation in the rest. Overall, 31 different sequence variations were identified, reported as mutations, polymorphisms and two novel variants, including: IVS1+1G>A, T8M, G12V, 35delG, V27I, M34T, V37I, E47X, 167delT, R75W, W77R, I82M, F83L, L90P, 269insT, V95M, 333delAA, R127H, E129K, R143W, V153I, G160S, M163V, M163L, K168R, R184P, C/T682 (3ÚTR), del(GJB6-D13S1830), del(GJB6-D13S1854). The mutation 35delG accounted for 13% of the patients, resulting in 37% of the detected mutations, being the most frequent causing mutation in our population, whether in homozygous state (16%), heterozygous (7%) or compound heterozygous (14%). Only 3% of mutations were detected in the GJB6 gene (del(GJB6-D13S1830) and del(GJB6-D13S1854)). All the other GJB2/GJB6 mutations show a very low carrier frequency. Conclusions: The present study demonstrates that different mutations in the GJB2 and GJB6 genes are present in our Argentinean population, and even though the 35delG is the most frequent one, a similar proportion of patients show pathogenic mutations different from 35delG. These findings strengthen the importance of genetic screening in hearing-impaired patients for the contribution towards an adequate genetic counseling and treatment planning.