{"id":112419,"date":"2018-03-11T10:39:20","date_gmt":"2018-03-11T10:39:20","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/aspectos-moleculares-de-la-enfermedad-de-mcardle\/"},"modified":"2018-03-11T10:39:20","modified_gmt":"2018-03-11T10:39:20","slug":"aspectos-moleculares-de-la-enfermedad-de-mcardle","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/aspectos-moleculares-de-la-enfermedad-de-mcardle\/","title":{"rendered":"Aspectos moleculares de la enfermedad de mcardle"},"content":{"rendered":"<h2>Tesis doctoral de <strong> In\u00e9s Garcia-consuegra Galiana <\/strong><\/h2>\n<p>Introducci\u00f3n:  la enfermedad de mcardle (glucogenosis tipo v) es un miopat\u00eda metab\u00f3lica de herencia autos\u00f3mica recesiva que se produce por un defecto en el gen pygm (11q13), que codifica para la isoforma muscular de la gluc\u00f3geno fosforilasa (gpm), en zima que inicia la degradaci\u00f3n del gluc\u00f3geno muscular con liberaci\u00f3n de glucosa-1-fosfato. Los pacientes presentan t\u00edpicamente intolerancia al ejercicio, mialgias y contracturas. Aproximadamente la mitad de los pacientes presentan mioglobinuria.  obj etivos: (1) genotipar una serie cl\u00ednica de 42 pacientes con d\u00e9ficit de gluc\u00f3geno fosforilasa muscular. (2) estudiar el mecanismo patog\u00e9nico de 6 nuevas mutaciones identificadas y la utilidad del arnm-pygm  en este tipo de estudios. (3) demostrar la e xistencia de amplificaci\u00f3n \u00c2\u00bfileg\u00edtima\u00c2\u00bf de los transcritos del gen pygm en sangre perif\u00e9rica y su posible aplicaci\u00f3n al diagn\u00f3stico molecular. (4) estudiar la relaci\u00f3n de la expresi\u00f3n proteica de gpm en homogenados musculares de pacientes con la enfer medad de mcardle. (5) analizar las interacciones de gpm con gluc\u00f3geno sintasa (gs) y serca1, prote\u00ednas reguladoras del metabolismo muscular, en tejido m\u00fasculo-esquel\u00e9tico de sujetos control y en pacientes con enfermedad de mcardle. resultados: en est e trabajo se han caracterizado molecularmente a 42 pacientes con la enfermedad de mcardle, siendo la mutaci\u00f3n p.R50x la m\u00e1s frecuente de la serie (52  frecuencia al\u00e9lica). Se identificaron 6 nuevas mutaciones: c.529-8g>a, c.(1969 214)_(2177 369)del, c.645g>a, c.2310_2311dupcc, c.407delg y c.1325t>a. Se ha confirmado la presencia del arnm del gen pygm mediante amplificaci\u00f3n \u00c2\u00bfileg\u00edtima\u00c2\u00bf del adnc de este gen obtenido a partir de sangre perif\u00e9rica total. No se ha logrado identificar la banda de 97 k da correspondiente al peso molecular de la isoforma muscular de la gpm, mediante la t\u00e9cnica de western blot en homogenados musculares correspondientes a 17 pacientes caracterizados tanto gen\u00e9tica como bioqu\u00edmicamente. Esta ausencia parece ser debida a la degradaci\u00f3n de la gpm alterada inmediatamente tras ser sintetizada. Esta ausencia total de prote\u00edna altera cualitativamente a la gluc\u00f3geno sintasa muscular (gs) y la serca1, ambas prote\u00ednas implicadas en el metabolismo del m\u00fasculo esquel\u00e9tico du rante el ejercicio. conclusiones: las siguientes conclusiones confirman y aportan consistencia a hallazgos previamente descritos de epidemiolog\u00eda molecular y relaci\u00f3n genotipo-fenotipo en la  enfermedad de mcardle: i) la mutaci\u00f3n p.R50x es la m\u00e1s fre<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Aspectos moleculares de la enfermedad de mcardle<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Aspectos moleculares de la enfermedad de mcardle <\/li>\n<li><strong>Autor:<\/strong>\u00a0 In\u00e9s Garcia-consuegra Galiana <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Complutense de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 24\/02\/2012<\/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>Miguel Angel Martin Casanueva<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: rafael Enr\u00edquez de salamanca lorente <\/li>\n<li>bel\u00e9n Bornstein s\u00e1nchez (vocal)<\/li>\n<li>carmen Navarro fern\u00e1ndez-balbuena (vocal)<\/li>\n<li>alejandro Luc\u00eda mulas (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de In\u00e9s Garcia-consuegra Galiana Introducci\u00f3n: la enfermedad de mcardle (glucogenosis tipo v) es un miopat\u00eda metab\u00f3lica de herencia [&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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