Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness, Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods: We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found. Results: Pathogenic mutations in GJB2 and GJB6 genes were detected in 41 individuals (13.7%), and 80.5% (33/41) presented these mutations in homozygosis or compound heterozygosis, thus explaining their hearing defect. The c.35delG in the GJB2 gene was the most frequent mutation (37/300; 12.4%), detected in 23% familial and 6.2% the sporadic cases. The second most frequent mutation (1%; 3/300) was the del(GJB6- D13S1830), always found associated with the c.35delG mutation. Nineteen different sequence variations were found in the GJB2 gene. In addition to the c.35delG mutation, nine known pathogenic alterations were detected 0 67delT, p.Trp24X, p.Val37lle, c.176_191del16, c.235delC, p.Leu90Pro, p.Arg127His, c.509insA, and p.Arg184Pro, Five substitutions had been previously considered benign polymorphisms: c.-15C>T, p.Val27lle, p.Met34hr, p.Ala40Ala, and p.Gly160Ser. Two previously reported Mutations of unknown pathogenicity were found (p.Lys168Arg, and c.684C>A), and two novel substitutions, p.Leu81Val (c.G241C) and p.Met195Val (c.A583G), both in heterozygosis without an accompanying mutation in the other allele. None of these latter four variants of undefined status was present in a sample of 100 hearing controls. Conclusions: The present study demonstrates that Mutations in the GJB2 gene and del(GJB6 D13S1830) are important causes of hearing impairment in Brazil, thus justifying their screening in a routine basis. The diversity of variants in our sample reflects the ethnic heterogeneity of the Brazilian population.

Effects of hearing protector devices on speech intelligibility

The purpose of this study was to determine the influence of hearing protection devices (HPDs) on the understanding of speech in young adults with normal hearing, both in a silent situation and in the presence of ambient noise. The experimental research was carried out with the following variables: five different conditions of HPD use (without protectors, with two earplugs and with two earmuffs); a type of noise (pink noise); 4 test levels (60, 70, 80 and 90 dB[A]); 6 signal/noise ratios (without noise, + 5, + 10, zero, - 5 and - 10 dB); 5 repetitions for each case, totalling 600 tests with 10 monosyllables in each one. The variable measure was the percentage of correctly heard words (monosyllabic) in the test. The results revealed that, at the lowest levels (60 and 70 dB), the protectors reduced the intelligibility of speech (compared to the tests without protectors) while, in the presence of ambient noise levels of 80 and 90 dB and unfavourable signal/noise ratios (0, -5 and -10 dB), the HPDs improved the intelligibility. A comparison of the effectiveness of earplugs versus earmuffs showed that the former offer greater efficiency in respect to the recognition of speech, providing a 30% improvement over situations in which no protection is used. As might be expected, this study confirmed that the protectors' influence on speech intelligibility is related directly to the spectral curve of the protector's attenuation. (C) 2003 Elsevier B.V. Ltd. All rights reserved.

Hearing loss in patients with diabetes mellitus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conductive hearing loss in children with bronchopulmonary dysplasia: A longitudinal follow-up study in children aged between 6 and 24 months

Aims: To determine the occurrence of isolated and recurrent episodes of conductive hearing loss (CHL) during the first two years of life in very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD).Study design, subjects and outcome measures: In a longitudinal clinical study. 187 children were evaluated at 6, 9, 12,15 18 and 24 months of age by visual reinforcement audiometry, tympanometry and auditory brain response system.Results: of the children with BPD, 54.5% presented with episodes of CHL, as opposed to 34.7% of the children without BPD. This difference was found to be statistically significant. The recurrent or persistent episodes were more frequent among children with BPD (25.7%) than among those without BPD (8.3%). The independent variables that contributed to this finding were small for gestational age and a 5 min Apgar score.Conclusions: Recurrent CHL episodes are more frequent among VLBW infants with BPD than among VLBW infants without BPD. (C) 2010 Elsevier B.V. All rights reserved.

Age impact on the eferent system actitivies in cochlear mechanical properties in normal hearing individuals

O trato olivococlear medial realiza o controle eferente das células ciliadas externas, regulando as contrações lentas e atenuando as rápidas. Com a pesquisa da amplitude das emissões otoacústicas sem e com estimulação acústica contra, ipsi ou bilateralmente, é possível estimar as condições desse trato, uma vez que o efeito resultante de redução/supressão das emissões indica seu funcionamento. O envelhecimento implica em diminuição da atividade do sistema auditivo central, em função da degeneração das estruturas envolvidas nas habilidades auditivas. OBJETIVO: O objetivo foi investigar o efeito da idade na atividade do trato sobre a cóclea, com a análise da amplitude das emissões com estimulação acústica contralateral. MATERIAL E MÉTODO: A casuística foi composta por 75 indivíduos agrupados conforme a idade. A metodologia foi o modo convencional, com clique linear e o ruído branco. ESTUDO DE CASO: A análise considerou a resposta das orelhas e a comparação entre os grupos. RESULTADOS: Os resultados revelam diferenças estatisticamente significantes entre o response das emissões sem e com estimulação acústica contralateral, nos indivíduos (20 a 39 anos). O efeito redução/supressão das emissões diminui com a idade (quarta década). CONCLUSÃO: O envelhecimento prejudica a efetividade da atividade do trato.

Incidence of self-reported hearing loss and associated risk factors among the elderly in São Paulo, Brazil: the SABE survey

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interventions to promote the wearing of hearing protection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Auditory steady state response in hearing assessment in infants with cytomegalovirus

OBJETIVO:Relatar o caso de um lactente com citomegalovírus congênito e disacusia neurossensorial progressiva, analisado por três métodos de avaliação auditiva.DESCRIÇÃO DO CASO:Na primeira avaliação auditiva, aos quatro meses de idade, o lactente apresentou ausência de Emissões Otoacústicas (EOA) e Potencial Evocado Auditivo de Tronco Encefálico (PEATE) dentro dos padrões de normalidade para a faixa etária, com limiar eletrofisiológico em 30dBnHL, bilateralmente. Com seis meses, apresentou ausência de PEATE bilateral em 100dBnHL. A avaliação comportamental da audição mostrou-se prejudicada devido ao atraso no desenvolvimento neuropsicomotor. Aos oito meses, foi submetido ao exame de Resposta Auditiva de Estado Estável (RAEE) e os limiares encontrados foram 50, 70, ausente em 110 e em 100dB, respectivamente para 500, 1.000, 2.000 e 4.000Hz, à direita, e 70, 90, 90 e ausente em 100dB, respectivamente para 500, 1.000, 2.000 e 4.000Hz, à esquerda.COMENTÁRIOS:Na primeira avaliação, o lactente apresentou alteração auditiva no exame de EOA e PEATE normal, que passou a ser alterado aos seis meses de idade. A intensidade da perda auditiva só pôde ser identificada pelo exame de RAEE, permitindo estabelecer a melhor conduta na adaptação de aparelho de amplificação sonora individual. Ressalta-se a importância do acompanhamento audiológico para crianças com CMV congênito.

Evaluation of hearing protection used by police officers in the shooting range

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Association between interleukin-6 polymorphism in the-174 G/C region and hearing loss in the elderly with a history of occupational noise exposure

Introduction: The biological processes involved in noise-induced hearing loss (NIHL) are still unclear. The involvement of inflammation in this condition has been suggested.Objective: To investigate the association between interleukin - 6 (IL-6) polymorphism and susceptibility to NIHL.Methods: This was a cross-sectional study with a sample of 191 independent elderly individuals aged >60 years of age. Information on exposure to occupational noise was obtained by interviews. Audiological evaluation was performed using pure tone audiometry and genotyped through PCR by restriction fragment length polymorphism - PCR-RFLP. Data were analyzed using the chi-square test and the odds ratio (OR), with the significance level set at 5%.Results: Among elderly with hearing loss (78.0%), 18.8% had a history of exposure to occupational noise. There was a statistically significant association between the genotype frequencies of the IL-6 - 174 and NIHL. The elderly with the CC genotype were less likely to have hearing loss due to occupational noise exposure when compared to those carrying the GG genotype (OR = 0.0124; 95% CI 0.0023-0.0671; p<0.001).Conclusion: This study suggests there is an association of polymorphisms in the IL-6 gene at position - G174C with susceptibility to noise-induced hearing loss. (C) 2014 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

P300 in individuals with sensorineural hearing loss

INTRODUCTION: Behavioral and electrophysiological auditory evaluations contribute to the understanding of the auditory system and of the process of intervention. OBJECTIVE: To study P300 in subjects with severe or profound sensorineural hearing loss. METHODS: This was a descriptive cross-sectional prospective study. It included 29 individuals of both genders with severe or profound sensorineural hearing loss without other type of disorders, aged 11 to 42 years; all were assessed by behavioral audiological evaluation and auditory evoked potentials. RESULTS: A recording of the P3 wave was obtained in 17 individuals, with a mean latency of 326.97 ms and mean amplitude of 3.76 V. There were significant differences in latency in relation to age and in amplitude according to degree of hearing loss. There was a statistically significant association of the P300 results with the degrees of hearing loss (p = 0.04), with the predominant auditory communication channels (p < 0.0001), and with time of hearing loss. CONCLUSIONS: P300 can be recorded in individuals with severe and profound congenital sensorineural hearing loss; it may contribute to the understanding of cortical development and is a good predictor of the early intervention outcome.

Neonatal hearing screening in a low-risk maternity in São Paulo state

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The importance of retesting the hearing screening as an indicator of the real early hearing disorder

Early diagnosis of hearing loss minimizes its impact on child development. We studied factors that influence the effectiveness of screening programs. To investigate the relationship between gender, weight at birth, gestational age, risk factors for hearing loss, venue for newborn hearing screening and pass and fail results in the retest. Prospective cohort study was carried out in a tertiary referral hospital. The screening was performed in 565 newborns through transient evoked otoacoustic emissions in three admission units before hospital discharge and retest in the outpatient clinic. Gender, weight at birth, gestational age, presence of risk indicators for hearing loss and venue for newborn hearing screening were considered. Full-term infants comprised 86% of the cases, preterm 14%, and risk factors for hearing loss were identified in 11%. Considering the 165 newborns retested, only the venue for screening, Intermediate Care Unit, was related to fail result in the retest. Gender, weight at birth, gestational age and presence of risk factors for hearing loss were not related to pass and/or fail results in the retest. The screening performed in intermediate care units increases the chance of continued fail result in the Transient Otoacoustic Evoked Emissions test.

Application of an auditory steady-state response test to evaluate the attenuation of hearing protection devices

This research aims to present a new method to get real attenuation of hearing protection devices, with good reproducibility and a small standard deviation, without relying on skills and cooperation individual. Thus the authors performed tests in 10 individuals without protection and after with two kinds of ear protections (ear plug and ear muffs), to get the threshold limit value in each of the 3 stages. For this, the research used an electrophysical exam, normally used in speech therapy, named ASSR (auditory steady-state response). The principle of this exam is put on individual’s head 3 electrodes, to capture electrical signs directly in auditory nerve. In summary, the authors presented the final results. The method proposed by ANSI (American National Standards Institute) indicated an attenuation of 27.6 dB for ear plugs, while the value found in this work was 16 dB; and for ear muffs, the ANSI method indicated 29.8 dB while the value found here was 28.5 dB.