Strategies for genetic study of hearing loss in the Brazilian northeastern region

The overall aim of this study was to estimate the contribution of genetic factors to the etiology of hearing loss (HL) in two counties in the Brazilian northeastern region. A cross-sectional study, based on the key informant approach (KI) was conducted in Queimadas and Gado Bravo counties (Paraíba, Northeast Brazil). The sample consisted of 182 patients with HL. Genetic screening of the most frequent mutations associated with HL was performed for all samples. DFNB1 mutations were the most frequently found in both counties. The c.35delG mutation was detected in homozygosis in seven non-syndromic probands in Queimadas (7/76, 9.2%) and only a single homozygote with this mutation was found in Gado Bravo (1/44, 2.3%). We also detected the del(GJB6-D13S1854) mutation in non-syndromic probands from Gado Bravo (2/44, 4.5%). The c.189C>A (p.TyrY63*) mutation in the CLRN1 gene was detected in homozygosis in 21/23 Usher syndrome patients from Gado Bravo and it was not found in Queimadas. Cases with probable genetic etiology contributed approximately to half of HL probands in each county (54.6% in Gado Bravo and 45.7% in Queimadas). We confirm the importance of DFNB1 locus to non-syndromic HL but we show that the frequency of mutations in the northeastern region differs somewhat from those reported in southeastern Brazil and other populations. In addition, the extremely high frequency of individuals with Usher syndrome with c.189C>A variation in CLRN1 indicates the need for a specific screening of this mutation.