Una nueva enfermedad genética retrasa el desarrollo del cerebro de los niños.
Los científicos han descubierto una nueva enfermedad genética que hace que el cerebro de algunos niños se desarrolle de manera anormal y retrasa el desarrollo intelectual.
La mayoría de los afectados por la enfermedad, que aún es tan nueva que carece de nombre, experimenta importantes desafíos educativos que repercuten negativamente en su calidad de vida.
Los cambios en un gen que codifica una proteína conocida como receptor ionotrópico del receptor de glutamato AMPA Tipo Subunidad 1 (GRIA1) fueron la causa subyacente de este trastorno genético poco común, según un equipo internacional de investigadores de universidades. PortsmouthY el Southampton, Y el Copenhague.
El descubrimiento de la variante ayudará a los médicos a desarrollar tratamientos enfocados para ayudar a los pacientes y sus familias y allanará el camino para la detección y el diagnóstico prenatales.
El gen GRIA1 facilita el movimiento de impulsos eléctricos dentro del cerebro. La capacidad del cerebro para recordar información puede verse afectada si se interfiere con este proceso o si se vuelve menos eficiente.
Para demostrar que las mutaciones GRIA1 son la causa principal de la enfermedad de cambio de comportamiento, el equipo de estudio, que consta de especialistas en genética de ranas, bioquímicos y genetistas clínicos, utilizó renacuajos en los que se transcribieron variaciones genéticas humanas mediante edición genética. También se realizó análisis bioquímico de variantes en huevos de rana.
Los resultados han sido publicados en Revista americana de genética humana.
El coautor del estudio, el profesor Matt Gill, quien dirige un laboratorio en el Grupo de Investigación de Epigenética y Biología del Desarrollo en[{» attribute=»»>University of Portsmouth, said: “Next generation DNA sequencing is transforming our ability to make new diagnoses and discover new genetic causes of rare disorders.
“The main bottleneck in providing diagnoses for these patients is linking a change discovered in their genome firmly to their disease. Making the suspect genetic change in tadpoles allows us to test whether it causes the same illness in humans.
“The resulting data allow us to support our colleagues in providing the more timely, accurate diagnosis that patients and their families so desperately need.”
Co-author Dr. Annie Goodwin, a Research Fellow at the University of Portsmouth who performed much of the study, said: “This was a transformational piece of work for us; the ability to analyze human-like behaviors in tadpoles with sufficient accuracy to detect genetic disease-linked changes opens the opportunity to help identify a huge range of diseases. This is particularly important given that so many neurodevelopmental diseases are currently undiagnosed.”
Co-author Professor Diana Baralle, Professor of Genomic Medicine and Associate Dean (Research) in the Faculty of Medicine at the University of Southampton added: “Discovering these new causes for genetic disorders ends our patients’ diagnostic odyssey and this has been made possible by collaborative interdisciplinary working across universities.”
One in 17 people will suffer from a rare disease at some time in their lives. Most of these rare diseases have a genetic cause and often affect children, but proving which gene change causes disease is a huge challenge.
Professor Guille said that previously, while studies connecting a gene and a disease were mainly performed in mice; several labs, including his own at the University of Portsmouth, have recently shown that experiments in tadpoles can also provide very strong evidence about the function of variant human genes. The process of re-creating some gene variants in tadpoles is straightforward and can be done in as little as three days.
Professor Guille added: “We are currently extending and improving our technology in a program funded by the Medical Research Council; this is making it applicable to the wider range of disease-related DNA changes provided to us by our clinical collaborators.
“If the clinical researchers find the information sufficiently useful, then we will continue to work together to scale up the pipeline of gene function analysis so it can be used to direct effective interventions for a significant number of patients.”
Reference: “Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome” by Vardha Ismail, Linda G. Zachariassen, Annie Godwin, Mane Sahakian, Sian Ellard, Karen L. Stals, Emma Baple, Kate Tatton Brown, Nicola Foulds, Gabrielle Wheway, Matthew O. Parker, Signe M. Lyngby, Miriam G. Pedersen, Julie Desir, Allan Bayat, Maria Musgaard, Matthew Guille, Anders S. Kristensen and Diana Baralle, 7 June 2022, American Journal of Human Genetics.
DOI: 10.1016/j.ajhg.2022.05.009
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