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

Emma Jenkinson; Mathieu P Rodero; Paul Kasher; Carolina Uggenti; Anthony Oojageer; Laurence Goosey; Yohann Rose; Jill Urquhart; Simon Williams; Sanjeev S Bhaskar; James O'Sullivan; Gabriela M Baerlocher; Monika Haubitz; Gerardine Aubert; Kristin W Barañano; Angela J Barnicoat; Roberta Battini; Andrea Berger; Edward M Blair; 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; Geraldine Quaghebeur; Raphael Schiffmann; Elliott H Sherr; Kanaga R Sinnathuray; Calvin Soh; Helen Stewart; John Stone; Hilde Van Esch; Christine E G Van Mol; Adeline Vanderver; Emma L Wakeling; Andrea Whitney; Graham Pavitt; Sam Griffiths-Jones; Gillian Rice; Patrick Revy; Marjo S van der Knaap; John H Livingston; Raymond O'Keefe; Yanick Crow; Christopher Kershaw

doi:10.1038/ng.3661

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

Emma Jenkinson, Mathieu P Rodero, Paul Kasher, Carolina Uggenti, Anthony Oojageer, Laurence Goosey, Yohann Rose, Jill Urquhart, Simon Williams, Sanjeev S Bhaskar, James O'Sullivan, Gabriela M Baerlocher, Monika Haubitz, Gerardine Aubert, Kristin W Barañano, Angela J Barnicoat, Roberta Battini, Andrea Berger, Edward M Blair, Janice E Brunstrom-HernandezJohannes 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, Geraldine Quaghebeur, Raphael Schiffmann, Elliott H Sherr, Kanaga R Sinnathuray, Calvin Soh, Helen Stewart, John Stone, Hilde Van Esch, Christine E G Van Mol, Adeline Vanderver, Emma L Wakeling, Andrea Whitney, Graham Pavitt, Sam Griffiths-Jones, Gillian Rice, Patrick Revy, Marjo S van der Knaap, John H Livingston, Raymond O'Keefe, Yanick Crow, Christopher Kershaw

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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 language	English
Pages (from-to)	1185–1192
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	10
Early online date	29 Aug 2016
DOIs	https://doi.org/10.1038/ng.3661
Publication status	Published - 19 Sept 2016

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Jenkinson, E., Rodero, M. P., Kasher, P., Uggenti, C., Oojageer, A., Goosey, L., Rose, Y., Urquhart, J., Williams, S., 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., ... Kershaw, C. (2016). Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nature Genetics, 48(10), 1185–1192. https://doi.org/10.1038/ng.3661

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title = "Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts",

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.",

author = "Emma Jenkinson and Rodero, {Mathieu P} and Paul Kasher and Carolina Uggenti and Anthony Oojageer and Laurence Goosey and Yohann Rose and Jill Urquhart and Simon Williams and Bhaskar, {Sanjeev S} and James O'Sullivan and Baerlocher, {Gabriela M} and Monika Haubitz and Gerardine Aubert and Bara{\~n}ano, {Kristin W} and Barnicoat, {Angela J} and Roberta Battini and Andrea Berger and Blair, {Edward M} and Brunstrom-Hernandez, {Janice E} and Buckard, {Johannes A} and Cassiman, {David M} and Rosaline Caumes and Cordelli, {Duccio M} and {De Waele}, {Liesbeth M} and Fay, {Alexander J} and Patrick Ferreira and Fletcher, {Nicholas A} and Fryer, {Alan E} and Himanshu Goel and Hemingway, {Cheryl A} and Marco Henneke and Imelda Hughes and Jefferson, {Rosalind J} and Ram Kumar and Lieven Lagae and Landrieu, {Pierre G} and Louren{\c c}o, {Charles M} and Malpas, {Timothy J} and Mehta, {Sarju G} and Imke Metz and Sakkubai Naidu and Katrin {\~O}unap and Axel Panzer and Prab Prabhakar and Geraldine Quaghebeur and Raphael Schiffmann and Sherr, {Elliott H} and Sinnathuray, {Kanaga R} and Calvin Soh and Helen Stewart and John Stone and {Van Esch}, Hilde and {Van Mol}, {Christine E G} and Adeline Vanderver and Wakeling, {Emma L} and Andrea Whitney and Graham Pavitt and Sam Griffiths-Jones and Gillian Rice and Patrick Revy and {van der Knaap}, {Marjo S} and Livingston, {John H} and Raymond O'Keefe and Yanick Crow and Christopher Kershaw",

year = "2016",

month = sep,

day = "19",

doi = "10.1038/ng.3661",

language = "English",

volume = "48",

pages = "1185–1192",

journal = "Nature Genetics",

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number = "10",

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Jenkinson, E, Rodero, MP, Kasher, P, Uggenti, C, Oojageer, A, Goosey, L, Rose, Y, Urquhart, J, Williams, S, 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, H, Stone, J, Van Esch, H, Van Mol, CEG, Vanderver, A, Wakeling, EL, Whitney, A, Pavitt, G , Griffiths-Jones, S , Rice, G, Revy, P, van der Knaap, MS, Livingston, JH, O'Keefe, R, Crow, Y & Kershaw, C 2016, 'Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts', Nature Genetics, vol. 48, no. 10, pp. 1185–1192. https://doi.org/10.1038/ng.3661

TY - JOUR

T1 - Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts

AU - Jenkinson, Emma

AU - Rodero, Mathieu P

AU - Kasher, Paul

AU - Uggenti, Carolina

AU - Oojageer, Anthony

AU - Goosey, Laurence

AU - Rose, Yohann

AU - Urquhart, Jill

AU - Williams, Simon

AU - Bhaskar, Sanjeev S

AU - O'Sullivan, James

AU - Baerlocher, Gabriela M

AU - Haubitz, Monika

AU - Aubert, Gerardine

AU - Barañano, Kristin W

AU - Barnicoat, Angela J

AU - Battini, Roberta

AU - Berger, Andrea

AU - Blair, Edward M

AU - Brunstrom-Hernandez, Janice E

AU - Buckard, Johannes A

AU - Cassiman, David M

AU - Caumes, Rosaline

AU - Cordelli, Duccio M

AU - De Waele, Liesbeth M

AU - Fay, Alexander J

AU - Ferreira, Patrick

AU - Fletcher, Nicholas A

AU - Fryer, Alan E

AU - Goel, Himanshu

AU - Hemingway, Cheryl A

AU - Henneke, Marco

AU - Hughes, Imelda

AU - Jefferson, Rosalind J

AU - Kumar, Ram

AU - Lagae, Lieven

AU - Landrieu, Pierre G

AU - Lourenço, Charles M

AU - Malpas, Timothy J

AU - Mehta, Sarju G

AU - Metz, Imke

AU - Naidu, Sakkubai

AU - Õunap, Katrin

AU - Panzer, Axel

AU - Prabhakar, Prab

AU - Quaghebeur, Geraldine

AU - Schiffmann, Raphael

AU - Sherr, Elliott H

AU - Sinnathuray, Kanaga R

AU - Soh, Calvin

AU - Stewart, Helen

AU - Stone, John

AU - Van Esch, Hilde

AU - Van Mol, Christine E G

AU - Vanderver, Adeline

AU - Wakeling, Emma L

AU - Whitney, Andrea

AU - Pavitt, Graham

AU - Griffiths-Jones, Sam

AU - Rice, Gillian

AU - Revy, Patrick

AU - van der Knaap, Marjo S

AU - Livingston, John H

AU - O'Keefe, Raymond

AU - Crow, Yanick

AU - Kershaw, Christopher

PY - 2016/9/19

Y1 - 2016/9/19

N2 - 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.

AB - 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.

U2 - 10.1038/ng.3661

DO - 10.1038/ng.3661

M3 - Article

C2 - 27571260

SN - 1546-1718

VL - 48

SP - 1185

EP - 1192

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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