Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.
Emma M JenkinsonMathieu P RoderoPaul R KasherCarolina UggentiAnthony OojageerLaurence C GooseyYoann RoseChristopher J KershawJill E UrquhartSimon G WilliamsSanjeev S BhaskarJames O'SullivanGabriela M BaerlocherMonika HaubitzGeraldine AubertKristin W BarañanoAngela J BarnicoatRoberta BattiniAndrea BergerEdward M BlairJanice E Brunstrom-HernandezJohannes A BuckardDavid M CassimanRosaline CaumesDuccio Maria CordelliLiesbeth M De WaeleAlexander J FayPatrick FerreiraNicholas A FletcherAlan E FryerHimanshu GoelCheryl A HemingwayMarco HennekeImelda HughesRosalind J JeffersonRam KumarLieven LagaePierre G LandrieuCharles Marques LourençoTimothy J MalpasSarju G MehtaImke MetzSakkubai NaiduKatrin ÕunapAxel PanzerPrab PrabhakarGerardine QuaghebeurRaphael SchiffmannElliott H SherrKanaga R SinnathurayCalvin SohHelen S StewartJohn StoneHilde Van EschChristine E G Van MolAdeline VanderverEmma L WakelingAndrea WhitneyGraham D PavittSam Griffiths-JonesGillian I RicePatrick RevyMarjo S van der KnaapJohn H LivingstonRaymond T O'KeefeYanick J CrowPublished in: Nature genetics (2016)
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.
Keyphrases
- binding protein
- subarachnoid hemorrhage
- transcription factor
- endothelial cells
- cerebral ischemia
- poor prognosis
- oxidative stress
- brain injury
- amino acid
- protein protein
- depressive symptoms
- big data
- dna binding
- intellectual disability
- blood brain barrier
- pluripotent stem cells
- autism spectrum disorder
- genome wide identification