{"id":4863,"date":"2023-03-05T09:06:01","date_gmt":"2023-03-05T09:06:01","guid":{"rendered":"https:\/\/neuropediatoolbox.org\/?p=4863"},"modified":"2023-12-29T18:33:15","modified_gmt":"2023-12-29T18:33:15","slug":"mutaciones-de-novo","status":"publish","type":"post","link":"https:\/\/neuropediatoolkit.org\/en\/mutaciones-de-novo\/","title":{"rendered":"Mutaciones \u00abde novo\u00bb."},"content":{"rendered":"\n

Durante los \u00faltimos a\u00f1os las mutaciones \u00abde novo\u00bb, aquellas no heredadas de ninguno de los dos progenitores, han cobrado especial relevancia en neurolog\u00eda pedi\u00e1trica, por varios motivos: <\/p>\n\n\n\n

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Son responsables de la mayor parte de los casos de trastornos del neurodesarrollo identificables gen\u00e9ticamente.<\/div><\/summary>
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Son responsables de los casos de mayor gravedad.<\/div><\/summary>
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Esto se explica porque existe sesgo por selecci\u00f3n natural. Las enfermedades heredadas suelen tener menor gravedad que las enfermedades \u00abde novo\u00bb, porque implican que el indiv\u00edduo ha sido capaz de vivir hasta la edad adulta, emparejase y reproducirse. De esta forma, las variantes que permanecen en la poblaci\u00f3n general, y son encontradas con frecuencia en portadores sanos, producen menor repercusi\u00f3n fenot\u00edpica, aunque que una variante sea \u00abde novo\u00bb no garantiza la patogenicidad.<\/p>\n\n\n\n

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<\/div>\n<\/div><\/details>\n\n\n\n
Cuestionan el paradigma cl\u00e1sico de enfermedad gen\u00e9tica como enfermedad heredada. <\/div><\/summary>
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Esto pone en cuesti\u00f3n la importancia relativa de los antecedentes familiares a la hora de sospechar una enfermedad gen\u00e9tica, ya que su ausencia no es criterio de exclusi\u00f3n. <\/p>\n\n\n\n

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El riesgo de mutaci\u00f3n de novo depende de la edad parental<\/a>. <\/div><\/summary>
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A trav\u00e9s de los estudios gen\u00f3micos, somos conocedores actualmente de que las personas sanas son portadoras de alrededor de unas 50-100 mutaciones de novo.<\/div><\/summary>
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Por lo tanto, no es infrecuente que existan casos de fenotipo complejo en los que m\u00faltiples mutaciones dan lugar a fenotipos superpuestos de mayor gravedad (double trouble<\/a>), dando lugar al concepto de \u00abcarga mutacional\u00bb. <\/div><\/summary>
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\"\"<\/figure>\n<\/div><\/details>\n\n\n\n
Esto cuestiona el paradigma cl\u00e1sico de enfermedad monogen\u00e9tica.<\/div><\/summary>
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De esta forma, el papel de las variantes gen\u00e9ticas que cada indiv\u00edduo presenta puede representar una herencia polig\u00e9nica (cuantitativa, factor de riesgo) cuando las variantes producen poca repercusi\u00f3n fenot\u00edpica, o una enfermedad monogen\u00e9tica, cuando la localizaci\u00f3n y consecuencias de la variante produce una repercusi\u00f3n cl\u00ednica grave.<\/p>\n\n\n\n

\"\"<\/figure>\n<\/div><\/details>\n<\/div>\n<\/div><\/details>\n<\/div>\n<\/div><\/details>\n\n\n\n
Pueden producirse m\u00e1s all\u00e1 de la concepci\u00f3n, por lo que son la causa de los mosaicismos constitucionales. <\/a><\/div><\/summary>
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