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1.
Med. infant ; 25(2): 165-173, Junio 2018. ilus
Artigo em Espanhol | LILACS | ID: biblio-909589

RESUMO

La hipoacusia congénita o de aparición temprana es un trastorno sensorial muy frecuente en niños. Las causas son diversas, pueden intervenir factores genéticos y/o ambientales. El 80% de la sordera hereditaria es no sindrómica y de herencia autosómica recesiva. Hasta un 50% de estos casos se deben a mutaciones en el locus DFNB1 donde están localizados los genes GJB2 y GJB6, que codifican las conexinas 26 y 30, dos proteínas que se expresan predominantemente en la cóclea. Se han reportado más de 100 mutaciones en el gen GJB2, con una mutación muy frecuente, 35delG, que representa hasta un 85% de los alelos mutados. Una deleción en el gen GJB6, (delGJB6-D13S1830), surge como la segunda mutación más frecuente. La hipoacusia debida a mutaciones en estos genes es de inicio prelocutivo, con un grado de severidad que varía de moderado a profundo, existiendo casos leves en menor proporción, con variaciones inter e intrafamiliares. Es generalmente estable, bilateral, y afecta a todas las frecuencias. El conocimiento de las causas genéticas de la hipoacusia ha permitido contar con nuevas herramientas para el diagnóstico, y como consecuencia, se ha optimizado el asesoramiento genético y facilitado el diagnóstico precoz de los pacientes, incluso en el período prenatal. La detección precoz tiene un impacto inmediato en la implementación de terapias que permiten una estimulación auditiva temprana. En esta revisión se describe el papel de las conexinas en la fisiología auditiva, así como también las características moleculares y audiológicas y el desempeño auditivo con audífonos e implante coclear en pacientes que presentan mutaciones en las conexinas 26 y 30.


Congenital or early appearing hearing loss is a very common sensory disorder in children. The causes for the disorder are diverse and genetic as well as environmental factors may be involved. Overall, 80% of the hereditary deafness is non-syndromic and of autosomal recessive inheritance. Up to 50% of the cases are associated with mutations in the DFNB1 locus that contains the GJB2 and the GJB6 genes encoding connexins 26 and 30, two proteins that are predominantly expressed in the cochlea. More than 100 mutations of the GJB2 have been reported. The 35delG is a common mutation accounting for up to 85% of the mutated alleles. A deletion in the GJB6 gene, (delGJB6-D13S1830), is the second most frequent mutation found. Hearing loss due to mutations in these genes has an onset before speech develops and degree of severity varies from moderate to severe, with a lower incidence of mild cases and inter- and intrafamily variations. The condition is usually stable, bilateral, and affecting all frequencies. Increased knowledge on the genetic causes of hearing loss has allowed for the development of new diagnostic tools and consequently, improvement of genetic counseling and early, even prenatal, diagnosis. Early detection has an immediate impact with implementation of early auditory stimulation therapies. In this review the role of connexins in auditory physiology described, as well as molecular and audiological features and auditory performance with hearing aids and cochlear implants in patients with connexins 26 and 30 mutations.


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Implante Coclear , Conexina 26 , Conexina 30 , Conexinas/genética , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Argentina/epidemiologia , Mutação , Patologia Molecular
2.
Braz. j. med. biol. res ; 51(9): e7560, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951752

RESUMO

We constructed lentiviral vectors containing the human wild-type GJB6 gene and the mutant variants A88V and G11R. The three proteins were stably expressed by the Tet-on system in the HaCaT cell line and used to study the functional effect of the variants. The CCK-8 assay and flow cytometric analyses were used to determine the levels of cell proliferation and apoptosis. Western blot analyses were performed to analyze the relevant clinical indicators of hidrotic ectodermal dysplasia and markers of apoptosis in transfected HaCaT cells. The CCK8 assay and the flow cytometry results showed a significant increase (P<0.05) in the apoptosis of HaCaT cells expressing the A88V and G11R mutants. In addition, we demonstrated that the A88V and G11R mutants induced the apoptosis of transfected HaCaT cells via the activation of caspase-3, -8, -9, and PARA. No change was observed in the activity of BAX compared with the control. This study provides further clarification on the mechanisms underlying the effect of the mutant variants A88V and G11R of the GJB6 gene on the induction of HaCaT cell apoptosis.


Assuntos
Humanos , Displasia Ectodérmica/genética , Apoptose/genética , Proliferação de Células/genética , Conexina 30/fisiologia , Mutação/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Doxiciclina/farmacologia , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo
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