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; 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 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

doi:10.1038/ng.3661

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, Gerardine Aubert, Kristin W Barañano, Angela J Barnicoat, Roberta Battini, Andrea Berger, Edward M BlairJanice 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 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 journal › Article › peer-review

Abstract / Description of output

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	8
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 - 31 Oct 2016

Keywords / Materials (for Non-textual outputs)

Adolescent
Adult
Calcinosis/genetics
Cell Line
Cerebral Small Vessel Diseases/genetics
Child
Child, Preschool
Chromosomes, Human, Pair 17
Cohort Studies
Cysts/genetics
Exome
Female
Genetic Linkage
Genome, Human
Humans
Infant
Leukoencephalopathies/genetics
Male
Middle Aged
Mutation
RNA, Small Nucleolar/genetics
Sequence Analysis, DNA
Young Adult

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Yanick Crow
- Deanery of Molecular, Genetic and Population Health Sciences - Chair of Genomic Medicine
- Centre for Genomic and Experimental Medicine
- Edinburgh Neuroscience
Person: Academic: Research Active

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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., ... Crow, Y. J. (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.",

keywords = "Adolescent, Adult, Calcinosis/genetics, Cell Line, Cerebral Small Vessel Diseases/genetics, Child, Child, Preschool, Chromosomes, Human, Pair 17, Cohort Studies, Cysts/genetics, Exome, Female, Genetic Linkage, Genome, Human, Humans, Infant, Leukoencephalopathies/genetics, Male, Middle Aged, Mutation, RNA, Small Nucleolar/genetics, Sequence Analysis, DNA, Young Adult",

author = "Jenkinson, {Emma M} and Rodero, {Mathieu P} and Kasher, {Paul R} and Carolina Uggenti and Anthony Oojageer and Goosey, {Laurence C} and Yoann Rose and Kershaw, {Christopher J} and Urquhart, {Jill E} and Williams, {Simon G} 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 Stewart, {Helen S} and John Stone and {Van Esch}, Hilde and {Van Mol}, {Christine E G} and Adeline Vanderver and Wakeling, {Emma L} and Andrea Whitney and Pavitt, {Graham D} and Sam Griffiths-Jones and Rice, {Gillian I} and Patrick Revy and {van der Knaap}, {Marjo S} and Livingston, {John H} and O'Keefe, {Raymond T} and Crow, {Yanick J}",

year = "2016",

month = oct,

day = "31",

doi = "10.1038/ng.3661",

language = "English",

volume = "48",

pages = "1185–1192",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

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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. 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 M

AU - Rodero, Mathieu P

AU - Kasher, Paul R

AU - Uggenti, Carolina

AU - Oojageer, Anthony

AU - Goosey, Laurence C

AU - Rose, Yoann

AU - Kershaw, Christopher J

AU - Urquhart, Jill E

AU - Williams, Simon G

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 S

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 D

AU - Griffiths-Jones, Sam

AU - Rice, Gillian I

AU - Revy, Patrick

AU - van der Knaap, Marjo S

AU - Livingston, John H

AU - O'Keefe, Raymond T

AU - Crow, Yanick J

PY - 2016/10/31

Y1 - 2016/10/31

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.

KW - Adolescent

KW - Adult

KW - Calcinosis/genetics

KW - Cell Line

KW - Cerebral Small Vessel Diseases/genetics

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 17

KW - Cohort Studies

KW - Cysts/genetics

KW - Exome

KW - Female

KW - Genetic Linkage

KW - Genome, Human

KW - Humans

KW - Infant

KW - Leukoencephalopathies/genetics

KW - Male

KW - Middle Aged

KW - Mutation

KW - RNA, Small Nucleolar/genetics

KW - Sequence Analysis, DNA

KW - Young Adult

U2 - 10.1038/ng.3661

DO - 10.1038/ng.3661

M3 - Article

C2 - 27571260

SN - 1061-4036

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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Yanick Crow

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