RESUMO
Auditory neuropathy is a hearing disorder characterized by normal outer hair cell function and abnormal neural conduction of the auditory pathway. Aetiology and clinical presentation of congenital or early-onset auditory neuropathy are heterogeneous, and their correlations are not well understood. Genetic backgrounds and associated phenotypes of congenital or early-onset auditory neuropathy were investigated by systematically screening a cohort of 23 patients from unrelated Japanese families. Of the 23 patients, 13 (56.5%) had biallelic mutations in OTOF, whereas little or no association was detected with GJB2 or PJVK, respectively. Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy. These results support the clinical significance of comprehensive mutation screening for auditory neuropathy.
Assuntos
Efeito Fundador , Estudos de Associação Genética/métodos , Perda Auditiva Central/epidemiologia , Perda Auditiva Central/genética , Proteínas de Membrana/genética , Adulto , Sequência de Aminoácidos , Povo Asiático/genética , Criança , Pré-Escolar , Conexina 26 , Conexinas/genética , Conexinas/metabolismo , Feminino , Testes Genéticos , Genótipo , Heterozigoto , Homozigoto , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Prevalência , Conformação Proteica , Análise de Sequência de DNARESUMO
1) The indices of hearing recovery for sudden deafness was examined. Because it did not reflect the severity of the initial hearing loss, the standard of the Japanese Ministry of Welfare was thought to be inadequate. 2) Since the prognosis of sudden deafness was known to be influenced by several factors, it seemed to be necessary for evaluating the efficacy of treatment to exclude various modifying factors. For this purpose predicting hearing recovery based on multiple regression analysis is appropriate. 3) The predicting recovery rate with the actual recovery rate for 4 kinds of treatment was compared. No significant difference was found between the expected values and the observed values. 4) The scatter diagram indicated 2 groups of patients. This might be due to different pathophysiology of sudden deafness. In the good recovery group, the recovery rate for prostaglandin E1 therapy was significantly better than the expected one.
Assuntos
Perda Auditiva Súbita/tratamento farmacológico , Adulto , Testes Auditivos , Humanos , Masculino , Análise Multivariada , Prognóstico , Análise de Regressão , Resultado do TratamentoAssuntos
Perda Auditiva , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Perda Auditiva de Alta Frequência , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de RegressãoRESUMO
In cases of sudden deafness (SD), hearing recovery is generally assessed by classifying recovery into four degrees. To evaluate factors that may affect the prognosis for hearing recovery (e.g., hearing level at initial examination, days elapsed from onset of hearing loss to start of treatment) or drug efficacy, however, a quantitative method would be more advantageous. In the present study, therefore, the recovery rate was used as an index in investigating the prognosis and the efficacy of steroid treatments in 183 patients with SD first examined within 14 days after the onset of hearing loss during the period 1980-85. As with the degree of hearing recovery, the recovery rate was found to be favorable in those patients with good hearing at the initial examination, no vertigo, little difference in high-tone and low-tone hearing loss, and only a short lag between onset of symptoms and the initiation of treatment. This indicated that the recovery rate could be used as an index for the evaluation of hearing recovery in cases of sudden deafness. The efficacy of steroid treatment was evaluated in patients in whom the average of the hearing levels at five frequencies from 250 to 4,000 Hz was 40-90 dB. No significant differences were found in either recovery rate or degree of recovery between those patients who received steroids and those who did not. This was believed to be attributable to the variety of pathological conditions involved in SD and to the influence of the other, non-steroidal drugs administered.