Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

Thomas A. Ravenscroft; Matt C. Baker; Nicola J. Rutherford; Manuela Neumann; Ian R. Mackenzie; Keith A. Josephs; Bradley F. Boeve; Ronald Petersen; Glenda M. Halliday; Jillian Kril; John C. van Swieten; William W. Seeley; Dennis W. Dickson; Rosa Rademakers

doi:10.1016/j.neurobiolaging.2013.04.004

Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

Thomas A. Ravenscroft, Matt C. Baker, Nicola J. Rutherford, Manuela Neumann, Ian R. Mackenzie, Keith A. Josephs, Bradley F. Boeve, Ronald Petersen, Glenda M. Halliday, Jillian Kril, John C. van Swieten, William W. Seeley, Dennis W. Dickson, Rosa Rademakers

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine-glycine-glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.

Original language	English (US)
Pages (from-to)	2235.e11-2235.e13
Journal	Neurobiology of aging
Volume	34
Issue number	9
DOIs	https://doi.org/10.1016/j.neurobiolaging.2013.04.004
State	Published - Sep 2013

Keywords

FET proteins
FUS
Frontotemporal lobar degeneration
PRMT1
PRMT3
PRMT8
Protein N-arginine methyltransferase

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2013.04.004

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Ravenscroft, T. A., Baker, M. C., Rutherford, N. J., Neumann, M., Mackenzie, I. R., Josephs, K. A., Boeve, B. F., Petersen, R., Halliday, G. M., Kril, J., van Swieten, J. C., Seeley, W. W., Dickson, D. W., & Rademakers, R. (2013). Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS. Neurobiology of aging, 34(9), 2235.e11-2235.e13. https://doi.org/10.1016/j.neurobiolaging.2013.04.004

Ravenscroft, TA, Baker, MC, Rutherford, NJ, Neumann, M, Mackenzie, IR, Josephs, KA , Boeve, BF , Petersen, R, Halliday, GM, Kril, J, van Swieten, JC, Seeley, WW, Dickson, DW & Rademakers, R 2013, 'Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS', Neurobiology of aging, vol. 34, no. 9, pp. 2235.e11-2235.e13. https://doi.org/10.1016/j.neurobiolaging.2013.04.004

@article{b25bc271808e4b3c82a874ffa0be3216,

title = "Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS",

abstract = "The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine-glycine-glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.",

keywords = "FET proteins, FUS, Frontotemporal lobar degeneration, PRMT1, PRMT3, PRMT8, Protein N-arginine methyltransferase",

author = "Ravenscroft, {Thomas A.} and Baker, {Matt C.} and Rutherford, {Nicola J.} and Manuela Neumann and Mackenzie, {Ian R.} and Josephs, {Keith A.} and Boeve, {Bradley F.} and Ronald Petersen and Halliday, {Glenda M.} and Jillian Kril and {van Swieten}, {John C.} and Seeley, {William W.} and Dickson, {Dennis W.} and Rosa Rademakers",

note = "Funding Information: This work is funded by a Mayo Benefactor and the Mayo Foundation . This work is further supported by the National Institute of Health grant no. P50 AG016574 , R01 NS065782 , R01 AG026251 , R01 AG037491 , P50 AG023501 , The Consortium for Frontotemporal Dementia Research and the Swiss National Science Foundation ( 31003A-132864 ). I.M. is supported by the Canadian Institutes of Health Research (grant # 74580 ) and the Pacific Alzheimer's Research Foundation ( C06-01 ). Tissues from Australia were received from the Sydney Brain Bank which is supported by the National Health and Medical Research Council of Australia , The University of New South Wales , and Neuroscience Research Australia . ",

year = "2013",

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doi = "10.1016/j.neurobiolaging.2013.04.004",

language = "English (US)",

volume = "34",

pages = "2235.e11--2235.e13",

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T1 - Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

AU - Ravenscroft, Thomas A.

AU - Baker, Matt C.

AU - Rutherford, Nicola J.

AU - Neumann, Manuela

AU - Mackenzie, Ian R.

AU - Josephs, Keith A.

AU - Boeve, Bradley F.

AU - Petersen, Ronald

AU - Halliday, Glenda M.

AU - Kril, Jillian

AU - van Swieten, John C.

AU - Seeley, William W.

AU - Dickson, Dennis W.

AU - Rademakers, Rosa

N1 - Funding Information: This work is funded by a Mayo Benefactor and the Mayo Foundation . This work is further supported by the National Institute of Health grant no. P50 AG016574 , R01 NS065782 , R01 AG026251 , R01 AG037491 , P50 AG023501 , The Consortium for Frontotemporal Dementia Research and the Swiss National Science Foundation ( 31003A-132864 ). I.M. is supported by the Canadian Institutes of Health Research (grant # 74580 ) and the Pacific Alzheimer's Research Foundation ( C06-01 ). Tissues from Australia were received from the Sydney Brain Bank which is supported by the National Health and Medical Research Council of Australia , The University of New South Wales , and Neuroscience Research Australia .

PY - 2013/9

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N2 - The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine-glycine-glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.

AB - The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine-glycine-glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.

KW - FET proteins

KW - FUS

KW - Frontotemporal lobar degeneration

KW - PRMT1

KW - PRMT3

KW - PRMT8

KW - Protein N-arginine methyltransferase

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JO - Neurobiology of aging

JF - Neurobiology of aging

IS - 9

ER -

Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

Abstract

Keywords

ASJC Scopus subject areas

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