{"id":95758,"date":"2009-03-09T00:00:00","date_gmt":"2009-03-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/causas-geneticas-de-las-sorderas-dfnb4-el-sindrome-de-pendred-y-la-sordera-no-sindromica-eva\/"},"modified":"2009-03-09T00:00:00","modified_gmt":"2009-03-09T00:00:00","slug":"causas-geneticas-de-las-sorderas-dfnb4-el-sindrome-de-pendred-y-la-sordera-no-sindromica-eva","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/causas-geneticas-de-las-sorderas-dfnb4-el-sindrome-de-pendred-y-la-sordera-no-sindromica-eva\/","title":{"rendered":"Causas gen\u00e9ticas de las sorderas dfnb4: el sindrome de pendred y la sordera no sindromica eva"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Alejandra Pera Rojas <\/strong><\/h2>\n<p>Resumen el s\u00edndrome de pendred (ps) y la sordera \u00c2\u00bfeva no sindr\u00f3mica\u00c2\u00bf est\u00e1n causados por mutaciones en el gen slc26a4. Ambas patolog\u00edas son recesivas, encontr\u00e1ndose en muchos casos un \u00fanico alelo slc26a4 mutado o ninguno. En este trabajo se ha llevado a cabo el an\u00e1lisis mutacional del gen slc26a4 en 235 pacientes no relacionados con hipoacusia y 214 individuos normo-oyentes, espa\u00f1oles. Se identificaron 35 alelos mutados distintos, de los cuales 10 son nuevos. La mutaci\u00f3n p.Q514k, es la m\u00e1s frecuente (16%; 6\/37 variantes al\u00e9licas en afectados), el an\u00e1lisis de haplotipos mostr\u00f3 un efecto fundador en espa\u00f1a. adem\u00e1s, se ha descrito la primera mutaci\u00f3n de novo (p.Q413p) en el gen slc26a4, en un paciente con ps; y se ha caracterizado por primera vez, los puntos de rotura de una deleci\u00f3n multiex\u00f3nica de 14 kb. Constatamos que los criterios utilizados para validar los cambios missense \u00c2\u00bfconservaci\u00f3n del residuo afectado en ort\u00f3logos slc26a4 e incidencia del cambio en poblaci\u00f3n control\u00c2\u00bf, son insuficientes. Realizamos un an\u00e1lisis funcional de 10 alelos missense identificados en la poblaci\u00f3n sorda espa\u00f1ola. Este estudio demostr\u00f3 la naturaleza patog\u00e9nica de 8 alelos y la naturaleza polimorfita del cambio p.L597s, descrito previamente como patog\u00e9nico. El an\u00e1lisis mutacional del gen slc26a4 en nuestros pacientes ha mostrado que la inactivaci\u00f3n de ambos alelos de dicho gen es la causa de la mayor\u00eda de los casos ps. tambi\u00e9n la sordera \u00c2\u00bfeva no sindr\u00f3mica\u00c2\u00bf est\u00e1 causada por la inactivaci\u00f3n de ambos alelos del gen slc26a4, aunque la proporci\u00f3n de casos ligados a dicho gen es baja. Por otro lado, vemos que no existe correlaci\u00f3n genotipo-fenotipo en dichas sorderas. En la muestra espa\u00f1ola, las sorderas dfnb4 representan un 3% de los casos de hipoacusias autos\u00f3micas recesivas. summary pendred\u00c2\u00bfs syndrome (ps) and \u00c2\u00bfno-syndromic eva\u00c2\u00bf are caused by mutations in the slc26a4 gene. Both disorders are recessive, and yet only one mutated slc26a4 allele, or no mutation, is identified in many cases. We carry out the slc26a4 mutational analysis of 235 spanish probands with hearing impairment and 214 normal-hearing individuals. We found 35 different mutated alleles, 10 of which are novel. The p.Q514k variant, was the most prevalent mutation (16%; 6\/37 allelic variants in affected individuals), the haplotype analysis showed a founder effect in spain. Furthermore, we describe for the first time a de novo mutation (p.Q413p) in slc26a4 gene, in a ps patient; and we characterized for the first time, the break points of a 14 kb multiexonic deletion. We confirmed the criteria used to validate missense mutations \u00c2\u00bflow incidence of mutation in control population and substitution of evolutionary conserved amino acids\u00c2\u00bf, are insufficient. We performed a functional assay of 10 missense alleles identified in the spanish population. This analysis revealed the pathogenic nature of 8 aleles and the polymorphic nature of p.L597s variant, previously described as pathogenic. the mutational analysis of our patients showed that most of the ps cases are caused by biallelic inactivation of slc26a4 gene. Also, the \u00c2\u00bfnonsindromic eva\u00c2\u00bf deafness is caused by inactivation of both alleles of slc26a4 gene, although the proportion of cases linked to this gene is low. On the other hand, we have seen that there is not genotype-phenotype correlation. in the spanish sample, dfnb4 deafness stands for 3% of autosomic recessive hearing impairments.Espa\u00f1ola 89<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Causas gen\u00e9ticas de las sorderas dfnb4: el sindrome de pendred y la sordera no sindromica eva<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Causas gen\u00e9ticas de las sorderas dfnb4: el sindrome de pendred y la sordera no sindromica eva <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Alejandra Pera Rojas <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 03\/09\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Manuela Villamar Lopez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jes\u00fas Cruces pinto <\/li>\n<li>Mar\u00eda  carmen Ayuso garcia (vocal)<\/li>\n<li>Jos\u00e9 Luis San millan lopez (vocal)<\/li>\n<li>eladio Andr\u00e9s Velasco sampedro (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Alejandra Pera Rojas Resumen el s\u00edndrome de pendred (ps) y la sordera \u00c2\u00bfeva no sindr\u00f3mica\u00c2\u00bf est\u00e1n causados [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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