Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts
Open accessAbstract
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.
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Causal nonprotein-coding variants were identified in SNORD118, confirming a clinical diagnosis of leukoencephalopathy with calcifications and cysts in LD_0807.
“Finally, causal nonprotein‐coding variants were identified in SNORD118 (OMIM:616663), confirming a clinical diagnosis of leukoencephalopathy with calcifications and cysts (OMIM:614561) in LD_0807.18”
From Genome sequencing in persistently unsolved white matter disorders (2020) · cites this paper as [18]
The Results (page unavailable) identify rare SNORD118 variants in patients with leukoencephalopathy with calcifications and cysts, and the Discussion (page unavailable) concludes that these variants cause the disease. Our copy does not identify LD_0807 or report variants confirming that individual's diagnosis (searched: LD_0807 and LD0807). (LLM, conf=0.87)
Experimental — accuracy not yet measuredSNORD118 variants were found as part of a targeted cohort study and concomitantly found in our genome sequencing cohort.
“SNORD118 variants were found as part of a targeted cohort study and concomitantly found in our genome sequencing cohort.18”
From Genome sequencing in persistently unsolved white matter disorders (2020) · cites this paper as [18]
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Research works printed but not linked: 30
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van der Knaap, M. S., & Bugiani, M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1739-1 · Cited by 403 · see citing works
Genome sequencing in persistently unsolved white matter disorders
Helman, G., Lajoie, B. R., Crawford, J., Takanohashi, A., Walkiewicz, M., Dolzhenko, E., Gross, A. M., Gainullin, V. G., Bent, S. J., Jenkinson, E. M., et al. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50957 · Cited by 39 · see citing works
Self-citation
- Authors
- Jenkinson, E. M., Rodero, M. P., Kasher, P. R., Uggenti, C., Oojageer, A., Goosey, L. C., Rose, Y., Kershaw, C. J., Urquhart, J. E., Williams, S. G., Bhaskar, S. S., O'Sullivan, J., Baerlocher, G. M., Haubitz, M., Aubert, G., Barañano, K. W., Barnicoat, A. J., Battini, R., Berger, A., Blair, E. M., Brunstrom-Hernandez, J. E., Buckard, J. A., Cassiman, D. M., Caumes, R., Cordelli, D. M., De Waele, L. M., Fay, A. J., Ferreira, P., Fletcher, N. A., Fryer, A. E., Goel, H., Hemingway, C. A., Henneke, M., Hughes, I., Jefferson, R. J., Kumar, R., Lagae, L., Landrieu, P. G., Lourenço, C. M., Malpas, T. J., Mehta, S. G., Metz, I., Naidu, S., Õunap, K., Panzer, A., Prabhakar, P., Quaghebeur, G., Schiffmann, R., Sherr, E. H., Sinnathuray, K. R., Soh, C., Stewart, H. S., Stone, J., Van Esch, H., Van Mol, C. E. G., Vanderver, A., Wakeling, E. L., Whitney, A., Pavitt, G. D., Griffiths-Jones, S., Rice, G. I., Revy, P., van der Knaap, M. S., Livingston, J. H., O'Keefe, R. T., & Crow, Y. J.
- Affiliations
- University of Manchester (GB)
- Hôpital Necker-Enfants Malades (FR)
- University of Bern (CH)
- BC Cancer Agency (CA)
- Great Ormond Street Hospital (GB)
- Klinikum Weiden (DE)
- Churchill Hospital (GB)
- St. Louis Children's Hospital (US)
- Evangelisches Krankenhaus Düsseldorf (DE)
- KU Leuven (BE)
- Hôpital Roger Salengro (FR)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Alberta Children's Hospital (CA)
- Walton Centre (GB)
- Liverpool Women's Hospital (GB)
- Hunter Genetics (AU)
- National Health Service (GB)
- Universitätsmedizin Göttingen (DE)
- Royal Berkshire Hospital (GB)
- Alder Hey Children's NHS Foundation Trust (GB)
- Bicêtre Hospital (FR)
- Universidade de São Paulo (BR)
- Addenbrooke's Hospital (GB)
- Kennedy Krieger Institute (US)
- Tartu University Hospital (EE)
- DRK Kliniken Berlin (DE)
- Oxford University Hospitals NHS Trust (GB)
- University of California, San Francisco (US)
- Wexham Park Hospital (GB)
- Salford Royal NHS Foundation Trust (GB)
- Children's National (US)
- London North West Healthcare NHS Trust (GB)
- University Hospital Southampton NHS Foundation Trust (GB)
- Leeds General Infirmary (GB)
- Corresponding author
- Crow, Yanick J
- ORCID
- Jenkinson, Emma M
- Rodero, Mathieu P
- Kasher, Paul R
- Uggenti, Carolina
- Oojageer, Anthony
- Kershaw, Christopher J
- Urquhart, Jill E
- Williams, Simon G
- Bhaskar, Sanjeev S
- Baerlocher, Gabriela M
- Haubitz, Monika
- Battini, Roberta
- Brunstrom-Hernandez, Janice E
- Cassiman, David M
- Cordelli, Duccio M
- Fay, Alexander J
- Ferreira, Patrick
- Fletcher, Nicholas A
- Goel, Himanshu
- Hemingway, Cheryl A
- Henneke, Marco
- Hughes, Imelda
- Kumar, Ram
- Lourenço, Charles M
- Mehta, Sarju G
- Metz, Imke
- Õunap, Katrin
- Panzer, Axel
- Prabhakar, Prab
- Schiffmann, Raphael
- Sherr, Elliott H
- Stewart, Helen S
- Vanderver, Adeline
- Wakeling, Emma L
- Whitney, Andrea
- Pavitt, Graham D
- Rice, Gillian I
- Revy, Patrick
- Livingston, John H
- O'Keefe, Raymond T
- Crow, Yanick J
- Venue
- Nature Genetics
- Published
- 2016-08-29
- Volume
- 48
- Issue
- 10
- Pages
- 1185-1192
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5045717
- OpenAlex
- W2514286461
- Cited by
- 148
- References
- 0
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 20 · 2023: 11 · 2022: 18 · 2021: 13 · 2020: 16 · 2019: 14 · 2018: 12 · 2017: 17 · 2016: 2 · 2015: 1
- FWCI
- 11.28
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-02-01)
- Open access
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- GRO (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- University of Michigan
- Wellcome Trust (104981, 097820/Z11/B, 097820)
- Newlife the Charity for Disabled Children
- Great Ormond Street Hospital Charity (V1212)
- Agence Nationale de la Recherche (ANR-10-IAHU- 01, ANR-10-IAHU-0001, 10-IAHU-01, ANR-10)
- Centre National de la Recherche Scientifique
- College of Pharmacy, University of Michigan
- Biotechnology and Biological Sciences Research Council (BB/M006565/1)
- National Heart, Lung, and Blood Institute
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- biallelic variants, small nucleolar RNA, ribosome biogenesis, non-coding RNA, monogenic disorders, cysts
- MeSH terms
- Adolescent, Adult, Calcinosis, Cell Line, Child, Child, Preschool, Chromosomes, Human, Pair 17, Cysts, Female, Humans, Infant, Genetic Linkage, Male, Middle Aged, Mutation, Cohort Studies, Genome, Human, Sequence Analysis, DNA, RNA, Small Nucleolar, Young Adult, Leukoencephalopathies, Cerebral Small Vessel Diseases, Exome
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