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

作者：Jenkinson Emma M; Rodero Mathieu P; Kasher Paul R; Uggenti Carolina; Oojageer Anthony; Goosey Laurence C; Rose Yoann; Kershaw Christopher J; Urquhart Jill E; Williams Simon G; Bhaskar Sanjeev S; O' Sullivan James; Baerlocher Gabriela M; Haubitz Monika; Aubert Geraldine; Baranano Kristin W; Barnicoat Angela J; Battini Roberta; Berger Andrea; Blair Edward M; Brunstrom Hernandez Janice E; Buckard Johannes A; Cassiman David M; Caumes Rosaline

来源：Nature Genetics, 2016, 48(10): 1185-1192.

DOI：10.1038/ng.3661

Although ribosomes are ubiquitous 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-coding 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.

• 出版日期2016-10