Molecular study of hearing loss in Minas Gerais, Brazil.

INTRODUCTION: Deafness is the most frequent sensory deficit in humans. Incidence is estimated at 4:1000 births in Brazil. Specific programs for clinical care of patients with hearing loss are still scarce in Brazil and the issue is an important public health problem. OBJECTIVE: To determine the frequency of 35delG and D13S1830 mutations in GJB2 and GJB6 genes respectively in patients with non-syndromic sensorineural hearing loss from Minas Gerais, Brazil. METHODS: This research involved 53 individuals, who were assessed by a questionnaire for predicting the possibility of non-syndromic deafness and for data collecting. Samples were tested for the presence of the 35delG mutation in GJB2 gene and D13S1830 in GJB6 gene by polymerase chain reaction and restriction enzyme digestion. RESULTS: Epidemiological research has shown that the majority of the subjects are unaware of the etiology and the pathogenesis of hearing loss. In 9 patients (16.98%), 35delG mutation was found in heterozygosis and the allele frequency was estimate to be around 8.5%. Although 9.61% of the patients reported having some degree of consanguinity between the parents and 12.08% reported other cases of deafness in their families, this mutation was not found in homozygosis. The D13S1830 mutation was not found in this study. CONCLUSION: This research describes for the first time the frequency of the 35delG and D13S1830 mutation in hearing-impaired individuals from Minas Gerais, Brazil, and the collected data reinforce the need for further studies in this population due to heterogeneity of hearing loss.

Mutation screening of TP53, CHEK2 and BRCA genes in patients at high risk for hereditary breast and ovarian cancer (HBOC) in Brazil.

BACKGROUND: Few studies related to hereditary breast and ovarian cancer syndrome (HBOC) have been conducted in Brazil, and they are restricted to only small areas of the country. Here, we report the mutation profile of BRCA1/2, CHEK2 and TP53 genes in a cohort from Minas Gerais state. METHODS: These genes from 44 patients at high risk for HBOC were screened through high-resolution melting and/or sequencing. The pathogenicity of the alterations was checked using ClinVar database and bioinformatics programs. RESULTS: In BRCA genes we identified 46 variants, 38 without clinical significance and 8 pathogenic mutations including a new pathogenic mutation in BRCA1 gene (c.4688_4694delACCTGGAinsG). The most prevalent pathogenic mutation was c.4829_4830delTG, in the BRCA2 gene. This mutation was not described in the Brazilian population up to now and in this study, it was described with a prevalence of 6.8%. The p.R337H mutation in TP53 gene was found in one patient clinically diagnosed as HBOC and without clinical criteria for Li-Fraumeni syndrome. In CHEK2 gene, the undescribed variant c.485A > G was found and it presents as probably pathogenic through in silico analyses. Pathogenic mutations were found in 29.5% of the patients, 11.3% in BRCA1, 15.9% in BRCA2 and 2.3% in TP53 gene. CONCLUSIONS: Brazilian population is one of the most heterogeneous in the world and the mutational profile knowledge of genes related to HBOC from different regions can contribute to the definition of more cost-effective strategies for the prevention, identification and treatment of cancer.