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

Emma M. Jenkinson, Mathieu P. Rodero, Paul R. Kasher, Carolina Uggenti, Anthony Oojageer, Laurence C. Goosey, Yoann Rose, Christopher J. Kershaw, Jill E. Urquhart, Simon G. Williams, Sanjeev S. Bhaskar, James O'Sullivan, Gabriela M. Baerlocher, Monika Haubitz, Geraldine Aubert, Kristin W. Barañano, Angela J. Barnicoat, Roberta Battini, Andrea Berger, Edward M. Blair & 46 others Janice E. Brunstrom-Hernandez, Johannes A. Buckard, David M. Cassiman, Rosaline Caumes, Duccio M. Cordelli, Liesbeth M. De Waele, Alexander J. Fay, Patrick Ferreira, Nicholas A. Fletcher, Alan E. Fryer, Himanshu Goel, Cheryl A. Hemingway, Marco Henneke, Imelda Hughes, Rosalind J. Jefferson, Ram Kumar, Lieven Lagae, Pierre G. Landrieu, Charles M. Lourenço, Timothy J. Malpas, Sarju G. Mehta, Imke Metz, Sakkubai Naidu, Katrin Õunap, Axel Panzer, Prab Prabhakar, Gerardine Quaghebeur, Raphael Schiffmann, Elliott H. Sherr, Kanaga R. Sinnathuray, Calvin Soh, Helen S. Stewart, John Stone, Hilde Van Esch, Christine E G Van Mol, Adeline Vanderver, Emma L. Wakeling, Andrea Whitney, Graham D. Pavitt, Sam Griffiths-Jones, Gillian I. Rice, Patrick Revy, Marjo S. Van Der Knaap, John H. Livingston, Raymond T. O'Keefe, Yanick J. Crow

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1185-1192
Number of pages8
JournalNature Genetics
Volume48
Issue number10
DOIs
StatePublished - Oct 1 2016

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Cerebral Small Vessel Diseases
Small Nucleolar RNA
Leukoencephalopathies
Ribosomes
Cysts
Mutation
Untranslated RNA
Biogenesis
Protein Binding
Blood Vessels
Homeostasis
Phenotype
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Jenkinson, E. M., Rodero, M. P., Kasher, P. R., Uggenti, C., Oojageer, A., Goosey, L. C., ... Crow, Y. J. (2016). Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nature Genetics, 48(10), 1185-1192. DOI: 10.1038/ng.3661

Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. / 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; 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, Gerardine; 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.

In: Nature Genetics, Vol. 48, No. 10, 01.10.2016, p. 1185-1192.

Research output: Contribution to journalArticle

Jenkinson, EM, Rodero, MP, Kasher, PR, Uggenti, C, Oojageer, A, Goosey, LC, Rose, Y, Kershaw, CJ, Urquhart, JE, Williams, SG, Bhaskar, SS, O'Sullivan, J, Baerlocher, GM, Haubitz, M, Aubert, G, Barañano, KW, Barnicoat, AJ, Battini, R, Berger, A, Blair, EM, Brunstrom-Hernandez, JE, Buckard, JA, Cassiman, DM, Caumes, R, Cordelli, DM, De Waele, LM, Fay, AJ, Ferreira, P, Fletcher, NA, Fryer, AE, Goel, H, Hemingway, CA, Henneke, M, Hughes, I, Jefferson, RJ, Kumar, R, Lagae, L, Landrieu, PG, Lourenço, CM, Malpas, TJ, Mehta, SG, Metz, I, Naidu, S, Õunap, K, Panzer, A, Prabhakar, P, Quaghebeur, G, Schiffmann, R, Sherr, EH, Sinnathuray, KR, Soh, C, Stewart, HS, Stone, J, Van Esch, H, Van Mol, CEG, Vanderver, A, Wakeling, EL, Whitney, A, Pavitt, GD, Griffiths-Jones, S, Rice, GI, Revy, P, Van Der Knaap, MS, Livingston, JH, O'Keefe, RT & Crow, YJ 2016, 'Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts' Nature Genetics, vol 48, no. 10, pp. 1185-1192. DOI: 10.1038/ng.3661
Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC et al. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nature Genetics. 2016 Oct 1;48(10):1185-1192. Available from, DOI: 10.1038/ng.3661

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; 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, Gerardine; 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. / Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.

In: Nature Genetics, Vol. 48, No. 10, 01.10.2016, p. 1185-1192.

Research output: Contribution to journalArticle

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