Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts

Although ribosomes are ubiquitously expressed and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein...

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Detalles Bibliográficos
Autores principales: Jenkinson, Emma M., Rodero, Mathieu P., Kasher, Paul R., Uggenti, Carolina, Oojageer, Anthony, Goosey, Laurence C., Rose, Yohann, Kershaw, Christopher J., Urquhart, Jill E., Williams, Simon G., Bhaskar, Sanjeev S., O’Sullivan, James, Baerlocher, Gabriela M., Haubitz, Monika, Aubert, Geraldine, Barañano, Kristin W., Barnicoat, Angela J., Battini, Roberta, Berger, Andrea, Blair, Edward M., Brunstrom-Hernandez, Janice E., Buckard, Johannes A., Cassiman, David M., Caumes, Rosaline, Cordelli, Duccio M., De Waele, Liesbeth M., Fay, Alexander J., Ferreira, Patrick, Fletcher, Nicholas A., Fryer, Alan E., Goel, Himanshu, Hemingway, Cheryl A., Henneke, Marco, Hughes, Imelda, Jefferson, Rosalind J., Kumar, Ram, Lagae, Lieven, Landrieu, Pierre G., Lourenço, Charles M., Malpas, Timothy J., Mehta, Sarju G., Metz, Imke, Naidu, Sakkubai, Õunap, Katrin, Panzer, Axel, Prabhakar, Prab, Quaghebeur, Geraldine, Schiffmann, Raphael, Sherr, Elliott H., Sinnathuray, Kanaga R., Soh, Calvin, Stewart, Helen S., Stone, John, Van Esch, Hilde, Van Mol, Christine E.G., Vanderver, Adeline, Wakeling, Emma L., Whitney, Andrea, Pavitt, Graham D., Griffiths-Jones, Sam, Rice, Gillian I., Revy, Patrick, van der Knaap, Marjo S., Livingston, John H., O’Keefe, Raymond T., Crow, Yanick J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045717/
https://www.ncbi.nlm.nih.gov/pubmed/27571260
http://dx.doi.org/10.1038/ng.3661
Descripción
Sumario:Although ribosomes are ubiquitously expressed and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein encoding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis.

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