Connexin 26 variants and auditory neuropathy/dys‐synchrony among children in schools for the deaf

Cheng, Xing; Li, Li; Brashears, Shanda; Morlet, Thierry; Ng, San San; Berlín, Charles I.; Hood, Linda J.; Keats, Bronya J.B.

doi:10.1002/ajmg.a.30929

Cited by 51 publications

(48 citation statements)

References 44 publications

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“…Audiological examination of patients carrying GJB2 mutations exhibit reduced or missing distortion product oto-acoustic emissions (DPOAEs; Engel-Yeger et al 2002;Engel-Yeger et al 2003;Medica et al 2005;Morell et al 1998) although not in every case (Cheng et al 2005;Santarelli et al 2008). As reduction of the DPOAE is a sign of non-functional OHCs, such finding suggests that the underlying pathology in this case might be reduced OHC electromotility, essential for the active amplification of sound as shown by animal experiments where the 'motor' protein has been deleted (Liberman et al 2002) or reduced (Cheatham et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Reduced Electromotility of Outer Hair Cells Associated with Connexin-Related Forms of Deafness: An In silico Study of a Cochlear Network Mechanism

Mistrík¹,

Ashmore²

2010

JARO

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Mutations in the GJB2 gene encoding for the connexin 26 (Cx26) protein are the most common source of nonsyndromic forms of deafness. Cx26 is a building block of gap junctions (GJs) which establish electrical connectivity in distinct cochlear compartments by allowing intercellular ionic (and metabolic) exchange. Animal models of the Cx26 deficiency in the organ of Corti seem to suggest that the hearing loss and the degeneration of outer hair cells (OHCs) and inner hair cells is due to failed K + and metabolite homeostasis. However, OHCs can develop normally in some mutants, suggesting that the hair cells death is not the universal mechanism. In search for alternatives, we have developed an in silico large scale three-dimensional model of electrical current flow in the cochlea in the small signal, linearised, regime. The effect of mutations was analysed by varying the magnitude of resistive components representing the GJ network in the organ of Corti. The simulations indeed show that reduced GJ conductivity increases the attenuation of the OHC transmembrane potential at frequencies above 5 kHz from 6.1 dB/decade in the wild-type to 14.2 dB/decade. As a consequence of increased GJ electrical filtering, the OHC transmembrane potential is reduced by up to 35 dB at frequencies 910 kHz. OHC electromotility, driven by this potential, is crucial for sound amplification, cochlear sensitivity and frequency selectivity. Therefore, we conclude that reduced OHC electromotility may represent an additional mechanism underlying deafness in the presence of Cx26 mutations and may explain lowered OHC functionality in particular reported Cx26 mutants.

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Section: Introductionmentioning

confidence: 99%

Reduced Electromotility of Outer Hair Cells Associated with Connexin-Related Forms of Deafness: An In silico Study of a Cochlear Network Mechanism

Mistrík¹,

Ashmore²

2010

JARO

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“…However, there is no scientific evidence to support the real relationship between AN and mutations in the connexin 26 gene. Two studies detected mutations in this gene among patients with AN [43][44][45] .…”

Section: Discussionmentioning

confidence: 99%

Satisfaction of Children with Auditory Neuropathy and Cochlear Implant

Carvalho

Zago²,

Ramos³

et al. 2016

Int Adv Otol

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OBJECTIVE:In auditory neuropathy (AN) a dyssynchrony in the nerve conduction of the auditory nerve fibers is observed. Typically, patients with AN exhibit moderate to profound sensorineural hearing loss, and treatment using cochlear implants (CIs) or hearing aids should be performed as early as possible for a better hearing rehabilitation. The aim of this study is to evaluate the satisfaction level of patients with AN spectrum disorder treated using CIs. The Satisfaction with Amplification in Daily Life questionnaire was selected to evaluate 10 patients with AN treated using CIs. MATERIAL and METHODS:Clinical study of patients with AN spectrum disorder submitted to CI. A retrospective data analysis, genetic and clinical evaluation in a tertiary referral center was done. RESULTS:The means of the subscales for positive effects, services and costs, negative factors, and personal image were 6.15, 4.6, 3.26, and 3.33, respectively. CONCLUSIONS:Patients with AN treated using CIs consider themselves satisfied.

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“…Em recém--nascidos, diversos fatores como prematuridade, hiperbilirrubinemia, hipercolesterolemia, hipóxia, imaturidade do sistema nervoso central, baixo peso ao nascer, condições idiopáticas, fatores genéticos e ainda outros foram propostos como contribuintes, isoladamente ou em combinação, para o desenvolvimento de NA. [3][4][5][6] Estão propostas diversas teorias no que diz respeito aos locais de lesão auditiva que cursam com NA, tais como a membrana tectorial, as células ciliadas internas (CCI), as células ciliadas externas (CCE), alterações da liberação de neurotransmissores nas sinapses entre as células ciliadas internas e as fibras dos neurónios do gânglio espiral, alterações na transmissão elétrica das fibras do nervo coclear, problemas axonais diversos ou mesmo relacionados à mielinização do nervo coclear. 7 A prevalência descrita da NA em doentes pediátricos com hipoacúsia severa ou profunda é de cerca de 13,4%.…”

Section: Introductionunclassified

“…8 De entre os fatores genéticos, muito estudados, estão estabelecidas algumas mutações em genes classicamente descritos e relacionados com a NA, como o OTOF e o PJVAK. 4 Acredita-se que tais genes possam ser responsáveis por disfunções relacionadas com as CCI. 9 Estão já mapeados quatro loci considerados na literatura médica como responsáveis pela NA em doentes não--sindrómicos, de entre os quais: DFNB9 (OTOF) e DFNB59 (PJVK) para casos autossómicos recessivos; AUNA1 (DIA-PH3) em casos autossómicos dominantes; 1 AUNX1 em casos ligados ao X.…”

Section: Introductionunclassified

“…[10][11][12][13][14][15] Apesar de estarem descritos casos clássicos de NA em doentes com o diagnóstico genético molecular de homozigotia da mutação 35delG no gene GJB2, a associação entre mutações de GJB2 e NA foi abordada ainda em poucos trabalhos, não estando estabelecida uma correlação. 4,16 Na sua evolução, a perda auditiva pode ocorrer em graus variados, frequentemente com alterações na inteligibilidade da fala associadas a alterações nos exames eletrofisiológicos auditivos.…”

Section: Introductionunclassified

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Neuropatia Auditiva: Avaliação Clínica e Abordagem Diagnóstica

Carvalho¹,

Leão²,

Ramos³

et al. 2016

Acta Med Port

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RESUMOIntrodução: A neuropatia auditiva é uma condição na qual há alteração na condução neuronal do estímulo sonoro. Este trabalho pretende descrever e caracterizar a casuística de doentes com neuropatia auditiva. Material e Métodos:Realizámos um estudo transversal, retrospetivo, com descrição de uma série de casos consecutivos. O diagnóstico da neuropatia auditiva foi definido nas seguintes situações: Presença de otoemissões acústicas com potenciais auditivos de tronco encefálico ausente ou anormal e presença do microfonismo coclear independentemente da presença de otoemissões acústicas. Resultados:Foram avaliados 34 doentes com perda auditiva bilateral, 67% deles do sexo masculino. O aparecimento dos sintomas foi congênito em 80% dos casos. Na pesquisa das otoemissões acústicas, 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. Discussão:A literatura médica ainda apresenta grande variabilidade nos achados relacionados com a neuropatia auditiva, tanto na sua etiologia quanto nos dados epidemiológicos. Conclusão:A neuropatia auditiva apresenta um amplo espectro de alterações que podem resultar em disfunções leves a severas no funcionamento da via auditiva. Na nossa amostra, observámos que 80% das neuropatias auditivas terão tido origem congênita e/ou apresenta microfonismo coclear, 91% dos doentes apresenta défice auditivo significativo e 53% sofrem de surdez severa ou profunda. Palavras-chave: Células Ciliadas Auditivas; Células Ciliadas Auditivas Externas; Células Ciliadas Auditivas Internas; Potenciais Evocados Auditivos do Tronco Encefálico; Neuropatia Auditiva. ABSTRACT Introduction: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 patients' series within the clinical spectrum of auditory neuropathy. Material and Methods: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.Results: 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.Discussion: Medical literature shows great variability in findings related to auditory neuropathy, both in its etiology and epidemiological data. Conclusion: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 patient...

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Connexin 26 variants and auditory neuropathy/dys‐synchrony among children in schools for the deaf

Cited by 51 publications

References 44 publications

Reduced Electromotility of Outer Hair Cells Associated with Connexin-Related Forms of Deafness: An In silico Study of a Cochlear Network Mechanism

Reduced Electromotility of Outer Hair Cells Associated with Connexin-Related Forms of Deafness: An In silico Study of a Cochlear Network Mechanism

Satisfaction of Children with Auditory Neuropathy and Cochlear Implant

Neuropatia Auditiva: Avaliação Clínica e Abordagem Diagnóstica

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