Esta investigación pionera abre la vía para entender mejor las causas de este trastorno y posibilitar aproximaciones terapéuticas personalizadas
Investigadores del Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CiMUS), de la Universidad de Santiago de Compostela, han participado en la mayor secuenciación de exoma –la parte funcional del genoma- del trastorno del espectro autista (TEA) a nivel internacional.
El grupo Genomics and Bioinformatics del CIMUS, dirigido por Ángel Carracedo, ha colaborado como parte del Consorcio de Secuenciación del Autismo en este estudio publicado en «Cell» que implica el análisis de 35.584 personas, 11.986 de ellas con autismo.
A través de técnicas de secuenciación y análisis bioinformático, disciplinas fundamentales para lograr la máxima precisión, alcance y rapidez en los avances científicos y médicos, se han identificado 102 genes de riesgo relacionados con el autismo, un trastorno con un importante componente genético, de los cuales 31 son genes de riesgo novedosos.
De ellos, 49 muestran frecuencias más altas de variantes disruptivas de novo en individuos determinados por retraso del desarrollo neurológico grave, mientras que 53 muestran frecuencias más altas en individuos con TEA; y se ha evidenciado que la comparación de casos de autismo con mutaciones en estos grupos revela diferencias fenotípicas.
Según explica Ángel Carracedo, «la mayor parte de estos genes se expresan muy precozmente en el desarrollo cerebral y tienen un papel importante en la regulación de la expresión génica y en la comunicación entre neuronas. De ellos, un 10% están en zonas donde existen variantes de número de copia que ya se sabe que están a menudo implicadas en trastornos de espectro autista».
A raíz de este estudio, en el que ha participado también el Hospital Gregorio Marañón de Madrid y la Fundación Pública Galega de Medicina Xenómica (IDIS) y que cuenta con pacientes gallegos incluidos en la muestra, gracias a la colaboración de las asociaciones de pacientes con TEA de Galicia y la Fundación María José Jove; se han correlacionado los hallazgos genómicos con datos de expresión a nivel de la corteza cerebral, lo que demuestra que numerosos genes asociados al trastorno se encuentran en neuronas maduras excitatorias o inhibitorias, lo que se relaciona con el fenotipo de los pacientes.
El análisis de la secuenciación del exoma ha evidenciado que las neuronas excitatorias tempranas y las interneuronas del cuerpo estriado son las más enriquecidas en TEA; y las únicas que no están enriquecidas significativamente son las células progenitoras de oligodendrocitos y astrocitos.
El profesor Carracedo explica al respecto que «todos los genes implicados en el proceso tienen papeles funcionales convergentes y patrones de expresión en la corteza cerebral, por lo que la hipótesis razonable que manejamos es que puedan interactuar y contribuir de forma asociada al riesgo de desarrollar la enfermedad».
Nuevas pistas
Esta contribución internacional al conocimiento de los mecanismos genéticos y funcionales asociados al TEA abre una nueva vía para entender mejor sus causas y posibilitar en el futuro aproximaciones terapéuticas personalizadas.
El Trastorno del Espectro Autista (TEA), una condición de desarrollo neurológico de inicio en la infancia caracterizada por un déficit de comunicación social y patrones de comportamiento o intereses restringidos y repetitivos, afecta a más de 1% de la población y su prevalencia sigue en aumento.
Múltiples estudios han demostrado una alta heredabilidad, en gran parte debido a una variación común; aunque las variantes raras son las que contribuyen al riesgo individual, pero sin embargo las preguntas fundamentales sobre el neurodesarrollo y la neurofisiología alteradas por el TEA, incluso cuándo ocurre, dónde y en qué tipos de células siguen sin resolverse, de ahí la necesidad de estudios como el actual.
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