42 research outputs found
Molecular Investigation In Children Candidates And Submitted To Cochlear Implantation.
Recent progresses in molecular biology have been made in the diagnosis of sensorineural hearing loss. The high prevalence of a connexin 26 gene mutation, and its easy identification have made the diagnosis possible. The most frequent gene mutation is called 35delG. The purpose of this study was to evaluate the prevalence of 35delG mutation in children submitted to cochlear implantation who had severe and profound hearing loss previously diagnosed as idiopathic. The study was done at the Cochlear Implantation Clinic of the Otolaryngology Department and at the Laboratório Genética Humana-CBMEG, UNICAMP-SP. 32 children with severe to profound sensorineural hearing loss were evaluated. The detection of the 35delG mutation was made by a allele-specific PCR, using primers and polymerase chain reaction. 69% had a normal exam, 12% were homozygous for the mutation, 19% of the cases were heterozygous. The 35delG mutation in heterozygous is not a cause of hearing loss. The data confirm the high prevalence of the 35delG mutation in nonsyndromic bilateral profound sensorineural hearing loss. It was also possible to diagnose the cause of hearing loss as genetic in a significant percentage of patients. That stresses the importance of the molecular investigation in those cases formerly classified as idiopathic.72333-
Neuropatia auditiva: avaliação clĂnica e abordagem diagnĂłstica
Auditory neuropathy is a condition in which there is a change in the neuronal transmission of the auditory stimuli. Our objective was to describe the patientsâ series within the clinical spectrum of auditory neuropathy. We designed a transversal, retrospective study, with a description of a consecutive case series. Auditory neuropathy was defined by the presence of acoustic otoemissions plus absent/abnormal auditory brainstem responses with cochlear microphonism. 34 patients with bilateral hearing loss, 23 males and 11 females, were included in the study. Eighty percent of the cases had congenital onset of hearing loss. Acoustic otoemissions were absent in 67% of them. Cochlear microfonism was present in 79% of all cases. Prenatal, perinatal or ambiental factors were present in 35.2% of the cases. Medical literature shows great variability in findings related to auditory neuropathy, both in its etiology and epidemiological data. Auditory neuropathy presents a broad spectrum of changes that may result from mild to severe changes in the functioning of the auditory pathway, and in our sample we observed that 80% of Auditory neuropathy have congenital onset of hearing loss and/or with cochlear microphonism identified. 91% of patients experience significant hearing impairment and 53% suffer from severe or profound deafness6353359CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - CNPQCOORDENAĂĂO DE APERFEIĂOAMENTO DE PESSOAL DE NĂVEL SUPERIOR - CAPESnĂŁo temnĂŁo temA neuropatia auditiva Ă© uma condição na qual hĂĄ alteração na condução neuronal do estĂmulo sonoro. Este trabalho pretende descrever e caracterizar a casuĂstica de doentes com neuropatia auditiva. RealizĂĄmos um estudo transversal, retrospetivo, com descrição de uma sĂ©rie de casos consecutivos. O diagnĂłstico da neuropatia auditiva foi definido nas seguintes situaçÔes: Presença de otoemissĂ”es acĂșsticas com potenciais auditivos de tronco encefĂĄlico ausente ou anormal e presença do microfonismo coclear independentemente da presença de otoemissĂ”es acĂșsticas. Foram avaliados 34 doentes com perda auditiva bilateral, 67% deles do sexo masculino. O aparecimento dos sintomas
foi congĂȘnito em 80% dos casos. Na pesquisa das otoemissĂ”es acĂșsticas, a resposta foi ausente em 67% dos doentes. O microfonismo coclear foi detetado em 79% dos doentes. Antecedentes gestacionais, perinatais ou ambientais relevantes estiveram presentes em 35,3% dos casos. A literatura mĂ©dica ainda apresenta grande variabilidade nos achados relacionados com a neuropatia auditiva, tanto na sua etiologia quanto nos dados epidemiolĂłgicos. A neuropatia auditiva apresenta um amplo espectro de alteraçÔes que podem resultar em disfunçÔes leves a severas no funcionamento da via auditiva. Na nossa amostra, observĂĄmos que 80% das neuropatias auditivas terĂŁo tido origem congĂȘnita e/ou apresenta microfonismo coclear, 91% dos doentes apresenta dĂ©fice auditivo significativo e 53% sofrem de surdez severa ou profunda
Etiological investigation of deafness in neonates screened in a universal newborn hearing screening program
Purpose to describe the results of etiology of deaf in neonates screened in a universal newborn hearing screening program. Methods a descriptive, cross-sectional and prospective study. The study included all newborns diagnosed with hearing loss identified in a universal newborn hearing screening program from August 2003 to December 2006. The etiology of deaf was determined after detailed anamnesis performed by the otorhinolaryngologist; survey of serological tests for toxoplasmosis, rubella, cytomegalovirus, herpes, syphilis and HIV; tomography of the temporal bone and genetic tests. Results 17 neonates were diagnosed with hearing loss in the period studied. 64.7% of cases presented as probable causes prenatal etiology, 29.4% perinatal causes and one child (5.9%) had unknown etiology. Of prenatal causes, 36.4% had confirmed genetic origin and 36.4% presumed etiology of heredity. We confirmed the presence of congenital infections in 18.2% of cases and one child (9%) had craniofacial anomalies as a possible etiology. The degree of hearing loss more frequently observed in the subjects studied was the profound (47.1%). Conclusion the increased occurrence of etiologies in this study was of prenatal origin, followed by perinatal origin.Objetivo descrever os resultados da investigação etiolĂłgica da deficiĂȘncia auditiva realizada em neonatos rastreados em um programa de triagem auditiva neonatal universal. MĂ©todos estudo descritivo, transversal e prospectivo. Foram incluĂdos no estudo todos os neonatos diagnosticados com deficiĂȘncia auditiva identificados em um programa de triagem auditiva neonatal universal no perĂodo de agosto de 2003 a dezembro de 2006. A provĂĄvel etiologia da deficiĂȘncia auditiva foi determinada apĂłs anamnese detalhada realizada pelo mĂ©dico otorrinolaringologista; pesquisa das sorologias para toxoplasmose, rubĂ©ola, citomegalovĂrus, herpes, sĂfilis e HIV; tomografia dos ossos temporais e exames genĂ©ticos. Resultados foram diagnosticados 17 sujeitos com deficiĂȘncia auditiva no perĂodo estudado. 64.7% dos casos estudados apresentaram como provĂĄvel etiologia causas prĂ©-natais, 29.4% causas peri-natais e um sujeito (5,9%) apresentou etiologia desconhecida. Das causas prĂ©-natais, 36.4% tiveram origem genĂ©tica confirmada e 36.4% etiologia presumida de hereditariedade. Foi confirmada a presença de infecçÔes congĂȘnitas em 18.2% dos casos e um sujeito (9%) apresentou anomalia craniofacial como provĂĄvel etiologia. O grau de perda auditiva mais frequente observado nos sujeitos estudados foi o profundo (47,1%). ConclusĂŁo a maior ocorrĂȘncia de etiologias observada neste estudo foram as de origem prĂ©-natal, seguida das de origem peri-natal.42242
Influence of glutathione s-transferase on the ototoxicity caused by aminoglycosides
The process of hair cell damage and death as a result of exposure to noise and ototoxins seems to be mediated by reactive oxygen species. AIM: To investigate the relationship between genetic polymorphisms in the Glutathione S-transferase and the susceptibility to hearing loss induced by aminoglycosides. MATERIALS AND METHODS: Null genotypes were analyzed by multiplex-PCR in the DNA samples from 50 patients and 72 controls. The patients were divided into 3 groups, 10 with hearing loss using aminoglycosides (group A), 20 with hearing loss without exposure to the drug (group B) and 20 hearing individuals who used the antibiotic (group C). STUDY DESIGN: Experimental. RESULTS: Polymorphisms in the GSTM1 and GSTT1 genes were found in 16% and 42% of patients and in 18% and 53% of the control group, respectively. After statistical analysis no significant difference was observed between the control groups and A (p=0.86) and (p=0.41), controls and B (p=0.27) and (p=0.24), controls and C (p=0.07) and (p=0.47), controls and A + C (p=0.09) and (p=0.47), C and A (p=0.32) and (p=0.75), GSTT1 and GSTM1, respectively. CONCLUSION: Our data show that polymorphisms in GSTM1 and GSTT1 genes have no influence on the ototoxicity of aminoglycosides.O processo de morte e danos em cĂ©lulas ciliadas devido Ă exposição ao ruĂdo e ototoxinas parece ser mediado por espĂ©cies reativas de oxigĂȘnio. OBJETIVO: Investigar a relação entre polimorfismos gĂȘnicos na Glutationa S-transferase e a susceptibilidade Ă deficiĂȘncia auditiva induzida pelos aminoglicosĂdeos. CASUĂSTICA E MĂTODO: GenĂłtipos nulos foram analisados por PCR-multiplex em amostras de DNA de 50 pacientes e 72 controles. Os pacientes foram divididos em trĂȘs grupos, sendo 10 com deficiĂȘncia auditiva e uso de aminoglicosĂdeos (grupo A), 20 com deficiĂȘncia auditiva sem exposição Ă droga (grupo B), e 20 ouvintes que utilizaram o antibiĂłtico (grupo C). FORMA DE ESTUDO: Experimental. RESULTADOS: Polimorfismos nos genes GSTT1 e GSTM1 foram encontrados em 16% e 42% dos pacientes e em 18% e 53% do grupo controle, respectivamente. ApĂłs a anĂĄlise estatĂstica nenhuma diferença significativa foi observada entre os grupos controle e A (p=0,86) e (p=0,41), controle e B (p=0,27) e (p=0,24), controle e C (p=0,07) e (p=0,47), controle e A+C (p=0,09) e (p=0,47), C e A (p=0,32) e (p=0,75), GSTT1 e GSTM1, respectivamente. CONCLUSĂO: Nossos dados demonstram que polimorfismos na GSTT1 e GSTM1 nĂŁo exercem influĂȘncia sobre a ototoxicidade dos aminoglicosĂdeos.30630
Molecular investigation in children candidates and submitted to cochlear implantation
AIM: recent progresses in molecular biology have been made in the diagnosis of sensorineural hearing loss. The high prevalence of a connexin 26 gene mutation, and its easy identification have made the diagnosis possible. The most frequent gene mutation is called 35delG. The purpose of this study was to evaluate the prevalence of 35delG mutation in children submitted to cochlear implantation who had severe and profound hearing loss previously diagnosed as idiopathic. METHOD: The study was done at the Cochlear Implantation Clinic of the Otolaryngology Department and at the LaboratĂłrio GenĂ©tica Humana-CBMEG, UNICAMP-SP. 32 children with severe to profound sensorineural hearing loss were evaluated. The detection of the 35delG mutation was made by a allele -specific PCR, using primers and polymerase chain reaction. RESULTS: 69% had a normal exam, 12% were homozygous for the mutation, 19% of the cases were heterozygous. The 35delG mutation in heterozygousity is not a cause of hearing loss. CONCLUSION: The data confirm the high prevalence of the 35delG mutation in nonsyndromic bilateral profound sensorineural hearing loss. It was also possible to diagnose the cause of hearing loss as genetic in a significant percentage of patients. That stresses the importance of the molecular investigation in those cases formerly classified as idiopathic.OBJETIVOS: recentes progressos obtidos na biologia molecular vĂȘm possibilitando a identificação da etiologia da surdez. A alta prevalĂȘncia de mutaçÔes no gene da conexina 26 e sua facilidade de estudo possibilitam o diagnĂłstico. A mutação mais freqĂŒente neste gene Ă© a chamada 35delG. O objetivo do presente trabalho foi averiguar a incidĂȘncia da mutação 35delG em crianças candidatas e submetidas ao implante coclear que tiveram a surdez diagnosticada como, supostamente idiopĂĄtica. MATERIAL E MĂTODO: Estudo realizado no Setor de Implantes Cocleares da Disciplina de Otorrinolaringologia e no LaboratĂłrio GenĂ©tica Humana-CBMEG, UNICAMP-SP. Foram avaliadas 32 crianças candidatas e usuĂĄrias de implante coclear, apresentando perda auditiva neurossensorial severa a profunda bilateral. Para a detecção da mutação 35delG foi utilizada a tĂ©cnica de PCR alelo-especĂfico (AS-PCR), usando primers e reação em cadeia da polimerase. RESULTADOS: 69% apresentaram exame normal, 12% foram homozigotos e 19% dos casos foram heterozigotos. A mutação 35delG em heterozigose nĂŁo diagnostica a causa da surdez apenas comprova que o paciente Ă© portador dessa mutação. CONCLUSĂO: No presente estudo, os dados obtidos confirmaram a alta prevalĂȘncia da mutação 35delG no gene GJB2 em casos de perda auditiva neurossensorial nĂŁo-sindrĂŽmica bilateral profunda, resultado que concorda com a literatura. Foi possĂvel, tambĂ©m, diagnosticar como genĂ©tica a causa da surdez em uma parcela significativa de crianças. Estes dados reforçam a importĂąncia do estudo molecular em pacientes com surdez de origem supostamente idiopĂĄtica, uma vez que esse exame possibilita esclarecer a etiologia da perda auditiva.33333
Screening Of Genetic Alterations Related To Non-syndromic Hearing Loss Using Massarray IplexÂź Technology.
Recent advances in molecular genetics have enabled to determine the genetic causes of non-syndromic hearing loss, and more than 100 genes have been related to the phenotype. Due to this extraordinary genetic heterogeneity, a large percentage of patients remain without any molecular diagnosis. This condition imply the need for new methodological strategies in order to detect a greater number of mutations in multiple genes. In this work, we optimized and tested a panel of 86 mutations in 17 different genes screened using a high-throughput genotyping technology to determine the molecular etiology of hearing loss. The technology used in this work was the MassARRAY iPLEXÂź platform. This technology uses silicon chips and DNA amplification products for accurate genotyping by mass spectrometry of previous reported mutations. The generated results were validated using conventional techniques, as direct sequencing, multiplex PCR and RFLP-PCR. An initial genotyping of control subjects, showed failures in 20 % of the selected alterations. To optimize these results, the failed tests were re-designed and new primers were synthesized. Then, the specificity and sensitivity of the panel demonstrated values above 97 %. Additionally, a group of 180 individuals with NSHL without a molecular diagnosis was screened to test the diagnostic value of our panel, and mutations were identified in 30 % of the cases. In 20 % of the individuals, it was possible to explain the etiology of the HL. Mutations in GJB2 gene were the most prevalent, followed by other mutations in in SLC26A4, CDH23, MT-RNR1, MYO15A, and OTOF genes. The MassARRAY technology has the potential for high-throughput identification of genetic variations. However, we demonstrated that optimization is required to increase the genotyping success and accuracy. The developed panel proved to be efficient and cost-effective, being suitable for applications involving the molecular diagnosis of hearing loss.168
Single Nucleotide Polymorphisms Of The Gjb2 And Gjb6 Genes Are Associated With Autosomal Recessive Nonsyndromic Hearing Loss.
Single nucleotide polymorphisms (SNPs) are important markers in many studies that link DNA sequence variations to phenotypic changes; such studies are expected to advance the understanding of human physiology and elucidate the molecular basis of diseases. The DFNB1 locus, which contains the GJB2 and GJB6 genes, plays a key role in nonsyndromic hearing loss. Previous studies have identified important mutations in this locus, but the contribution of SNPs in the genes has not yet been much investigated. The aim of this study was to investigate the association of nine polymorphisms located within the DFNB1 locus with the occurrence of autosomal recessive nonsyndromic hearing loss (ARNSHL). The SNPs rs3751385 (C/T), rs7994748 (C/T), rs7329857 (C/T), rs7987302 (G/A), rs7322538 (G/A), rs9315400 (C/T), rs877098 (C/T), rs945369 (A/C), and rs7333214 (T/G) were genotyped in 122 deaf patients and 132 healthy controls using allele-specific PCR. There were statistically significant differences between patients and controls, in terms of allelic frequencies in the SNPs rs3751385, rs7994748, rs7329857, rs7987302, rs945369, and rs7333214 (P < 0.05). No significant differences between the two groups were observed for rs7322538, rs9315400, and rs877098. Our results suggest that SNPs present in the GJB2 and GJB6 genes may have an influence on ARNSHL in humans.201531872
Hearing preservation and cochlear implants according to inner ear approach: multicentric evaluation
AbstractIntroductionElectroacoustic stimulation is an excellent option for people with residual hearing in the low frequencies, who obtain insufficient benefit with hearing aids. To be effective, the subject's residual hearing should be preserved during cochlear implant surgery.ObjectivesTo evaluate the hearing preservation in patients that underwent implant placement and to compare the results in accordance with the approach to the inner ear.Methods19 subjects underwent a soft surgical technique, and the electrode MED-EL FLEXâą EAS, designed to be atraumatic, was used. We evaluated pre- and postoperative tonal audiometric tests with an average of 18.4 months after implantation, to measure the rate of hearing preservation.Results17 patients had total or partial preservation of residual hearing; 5 had total hearing preservation and two individuals had no preservation of hearing. The insertion of the electrode occurred through a cochleostomy in 3 patients, and in 2 of these there was no hearing preservation; the other 16 patients experienced electrode insertion through a round window approach. All patients benefited from the cochlear implant, even those who are only using electrical stimulation.ConclusionThe hearing preservation occurred in 89.4% of cases. There was no significant difference between the forms of inner ear approach