Format

Send to

Choose Destination
Nat Genet. 2016 Oct;48(10):1185-92. doi: 10.1038/ng.3661. Epub 2016 Aug 29.

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

Author information

1
Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Evolution and Genomic Sciences, University of Manchester, Manchester, UK.
2
Laboratory of Neurogenetics and Neuroinflammation, INSERM UMR 1163, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France.
3
Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Molecular and Cellular Function, University of Manchester, Manchester, UK.
4
Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
5
Experimental Hematology, Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
6
Repeat Diagnostics, Inc., North Vancouver, British Columbia, Canada.
7
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
8
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
9
Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland, USA.
10
Department of Clinical Genetics, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
11
Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy.
12
Department of Neuropediatrics, Klinikum Weiden, Weiden, Germany.
13
Department of Neuropediatrics, Klinikum Harlaching, Munich, Germany.
14
Department of Clinical Genetics, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
15
CP Place, PLLC, Plano, Texas, USA.
16
Department of Neurology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
17
Department of Neuropediatrics, Sozialpädiatrisches Zentrum am EVK Düsseldorf, Düsseldorf, Germany.
18
Metabolic Center, Leuven University Hospitals and KU Leuven, Leuven, Belgium.
19
Department of Neuropediatrics, Hopital Roger Salengro, Lille, France.
20
Paediatric Neurology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.
21
Department of Paediatric Neurology, University Hospitals Leuven, Leuven, Belgium.
22
Department of Development and Regeneration, Paediatric Neurology, University of Leuven, Leuven, Belgium.
23
Division of Medical Genetics, Alberta Children's Hospital, Calgary, Alberta, Canada.
24
Department of Neurology, Walton Centre NHS Foundation Trust, Liverpool, UK.
25
Department of Clinical Genetics, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
26
Hunter Genetics, Hunter New England Local Health District, Waratah, New South Wales, Australia.
27
School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
28
Department of Paediatric Neurology, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
29
Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg August University, Göttingen, Germany.
30
Pediatric Neurology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
31
Dingley Specialist Children's Centre, Royal Berkshire Hospital, Reading, UK.
32
Department of Paediatric Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
33
Department of Paediatric Neurology, CHU Paris-Sud Bicetre, Le Kremlin Bicetre, France.
34
Neurogenetics Division, Clinics Hospital of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
35
Department of Paediatrics, Jersey General Hospital, St Helier, UK.
36
East Anglian Regional Genetics Service, Addenbrooke's Hospital, Cambridge, UK.
37
Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
38
Hugo Moser Research Institute, Kennedy Krieger Institute, Johns Hopkins Medical Institutions, Neurology and Pediatrics, Baltimore, Maryland, USA.
39
Department of Genetics, Tartu University Hospital, Tartu, Estonia.
40
Department of Pediatrics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
41
Epilepsy Center/Paediatric Neurology, DRK Kliniken Berlin-Westend, Berlin, Germany.
42
Department of Neuroradiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
43
Institute of Metabolic Disease, Baylor Research Institute, Dallas, Texas, USA.
44
Department of Neurology, University of California at San Francisco, San Francisco, California, USA.
45
Department of Paediatrics, Wexham Park Hospital, Slough, UK.
46
Neuroradiology Department, Salford Royal NHS Foundation Trust, Salford, UK.
47
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
48
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
49
Department of Pediatrics-Neonatology, St. Augustinusziekenhuis, Wilrijk, Belgium.
50
Department of Neurology, George Washington University School of Medicine, Children's National Health System, Washington, DC, USA.
51
Center for Genetic Medicine Research, George Washington University School of Medicine, Children's National Health System, Washington, DC, USA.
52
North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Harrow, UK.
53
Department of Child Neurology, University Hospital Southampton NHS Trust, Southampton, UK.
54
Laboratory of Genome Dynamics in the Immune System, INSERM UMR 1163, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France.
55
Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France.
56
Child Neurology and Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.
57
Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.
58
Department of Paediatric Neurology, Leeds General Infirmary, Leeds, UK.

Abstract

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.

PMID:
27571260
PMCID:
PMC5045717
DOI:
10.1038/ng.3661
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center