LRP10 variants in progressive supranuclear palsy

Leonie J.M. Vergouw; Shamiram Melhem; Laura Donker Kaat; Wang Z. Chiu; Demy J.S. Kuipers; Guido Breedveld; Agnita J.W. Boon; Li San Wang; Adam C. Naj; Elizabeth Mlynarksi; Laura Cantwell; Marialuisa Quadri; Owen A. Ross; Dennis W. Dickson; Gerard D. Schellenberg; John C. van Swieten; Vincenzo Bonifati; Frank Jan de Jong

doi:10.1016/j.neurobiolaging.2020.04.016

LRP10 variants in progressive supranuclear palsy

Leonie J.M. Vergouw, Shamiram Melhem, Laura Donker Kaat, Wang Z. Chiu, Demy J.S. Kuipers, Guido Breedveld, Agnita J.W. Boon, Li San Wang, Adam C. Naj, Elizabeth Mlynarksi, Laura Cantwell, Marialuisa Quadri, Owen A. Ross, Dennis W. Dickson, Gerard D. Schellenberg, John C. van Swieten, Vincenzo Bonifati, Frank Jan de Jong

Neuroscience

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

2 Scopus citations

Abstract

The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Two patients from the discovery cohort and 8 patients from the validation cohort carried a rare, heterozygous, and possibly pathogenic LRP10 variant (p.Gly326Asp, p.Asp389Asn, and p.Arg158His, p.Cys220Tyr, p.Thr278Ala, p.Gly306Asp, p.Glu486Asp, p.Arg554∗, p.Arg661Cys). In conclusion, possibly pathogenic LRP10 variants occur in a small fraction of patients with PSP and may be overrepresented in these patients compared with controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.

Original language	English (US)
Pages (from-to)	311.e5-311.e10
Journal	Neurobiology of aging
Volume	94
DOIs	https://doi.org/10.1016/j.neurobiolaging.2020.04.016
State	Published - Oct 2020

Keywords

Genetics
LRP10
Progressive supranuclear palsy
Rare variants

ASJC Scopus subject areas

Neuroscience(all)
Aging
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2020.04.016

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Vergouw, L. J. M., Melhem, S., Donker Kaat, L., Chiu, W. Z., Kuipers, D. J. S., Breedveld, G., Boon, A. J. W., Wang, L. S., Naj, A. C., Mlynarksi, E., Cantwell, L., Quadri, M., Ross, O. A., Dickson, D. W., Schellenberg, G. D., van Swieten, J. C., Bonifati, V., & de Jong, F. J. (2020). LRP10 variants in progressive supranuclear palsy. Neurobiology of aging, 94, 311.e5-311.e10. https://doi.org/10.1016/j.neurobiolaging.2020.04.016

Vergouw, LJM, Melhem, S, Donker Kaat, L, Chiu, WZ, Kuipers, DJS, Breedveld, G, Boon, AJW, Wang, LS, Naj, AC, Mlynarksi, E, Cantwell, L, Quadri, M, Ross, OA , Dickson, DW, Schellenberg, GD, van Swieten, JC, Bonifati, V & de Jong, FJ 2020, 'LRP10 variants in progressive supranuclear palsy', Neurobiology of aging, vol. 94, pp. 311.e5-311.e10. https://doi.org/10.1016/j.neurobiolaging.2020.04.016

@article{02e364cbfa6c4a4dbccf146945cc1440,

title = "LRP10 variants in progressive supranuclear palsy",

abstract = "The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Two patients from the discovery cohort and 8 patients from the validation cohort carried a rare, heterozygous, and possibly pathogenic LRP10 variant (p.Gly326Asp, p.Asp389Asn, and p.Arg158His, p.Cys220Tyr, p.Thr278Ala, p.Gly306Asp, p.Glu486Asp, p.Arg554∗, p.Arg661Cys). In conclusion, possibly pathogenic LRP10 variants occur in a small fraction of patients with PSP and may be overrepresented in these patients compared with controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.",

keywords = "Genetics, LRP10, Progressive supranuclear palsy, Rare variants",

author = "Vergouw, {Leonie J.M.} and Shamiram Melhem and {Donker Kaat}, Laura and Chiu, {Wang Z.} and Kuipers, {Demy J.S.} and Guido Breedveld and Boon, {Agnita J.W.} and Wang, {Li San} and Naj, {Adam C.} and Elizabeth Mlynarksi and Laura Cantwell and Marialuisa Quadri and Ross, {Owen A.} and Dickson, {Dennis W.} and Schellenberg, {Gerard D.} and {van Swieten}, {John C.} and Vincenzo Bonifati and {de Jong}, {Frank Jan}",

note = "Funding Information: The authors gratefully acknowledge support of patients and their families for participating in this study, the CurePSP Society, and the Human Genotyping Facility of the Genetic laboratory of the Department of Internal Medicine at the Erasmus Medical Center for the whole-exome sequencing service in the discovery cohort. This work was supported by a grant of ZonMw, Netherlands ( 70-73305-98-102 ) to FJdJ, and by grants from the Stichting Parkinson Fonds, Netherlands to VB. A subset of validation cohort samples included in this study were brain donors to the brain bank at Mayo Clinic in Jacksonville, which is supported by CurePSP and the Tau Consortium and in part by the Mayo Clinic Florida NINDS Tau Center without Walls Program (U54-NS100693) and the NIH sequencing project (UG3 NS104095). This work was also supported by grants from the NIA / NIH, United States ( P01 AG017586 ) and NINDS /NIH, United States ( U54 NS100693 ) to GDS and a grant from NIA/NIH ( R01 AG054060 ) to ACN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = oct,

doi = "10.1016/j.neurobiolaging.2020.04.016",

language = "English (US)",

volume = "94",

pages = "311.e5--311.e10",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - LRP10 variants in progressive supranuclear palsy

AU - Vergouw, Leonie J.M.

AU - Melhem, Shamiram

AU - Donker Kaat, Laura

AU - Chiu, Wang Z.

AU - Kuipers, Demy J.S.

AU - Breedveld, Guido

AU - Boon, Agnita J.W.

AU - Wang, Li San

AU - Naj, Adam C.

AU - Mlynarksi, Elizabeth

AU - Cantwell, Laura

AU - Quadri, Marialuisa

AU - Ross, Owen A.

AU - Dickson, Dennis W.

AU - Schellenberg, Gerard D.

AU - van Swieten, John C.

AU - Bonifati, Vincenzo

AU - de Jong, Frank Jan

N1 - Funding Information: The authors gratefully acknowledge support of patients and their families for participating in this study, the CurePSP Society, and the Human Genotyping Facility of the Genetic laboratory of the Department of Internal Medicine at the Erasmus Medical Center for the whole-exome sequencing service in the discovery cohort. This work was supported by a grant of ZonMw, Netherlands ( 70-73305-98-102 ) to FJdJ, and by grants from the Stichting Parkinson Fonds, Netherlands to VB. A subset of validation cohort samples included in this study were brain donors to the brain bank at Mayo Clinic in Jacksonville, which is supported by CurePSP and the Tau Consortium and in part by the Mayo Clinic Florida NINDS Tau Center without Walls Program (U54-NS100693) and the NIH sequencing project (UG3 NS104095). This work was also supported by grants from the NIA / NIH, United States ( P01 AG017586 ) and NINDS /NIH, United States ( U54 NS100693 ) to GDS and a grant from NIA/NIH ( R01 AG054060 ) to ACN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2020

PY - 2020/10

Y1 - 2020/10

N2 - The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Two patients from the discovery cohort and 8 patients from the validation cohort carried a rare, heterozygous, and possibly pathogenic LRP10 variant (p.Gly326Asp, p.Asp389Asn, and p.Arg158His, p.Cys220Tyr, p.Thr278Ala, p.Gly306Asp, p.Glu486Asp, p.Arg554∗, p.Arg661Cys). In conclusion, possibly pathogenic LRP10 variants occur in a small fraction of patients with PSP and may be overrepresented in these patients compared with controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.

AB - The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Two patients from the discovery cohort and 8 patients from the validation cohort carried a rare, heterozygous, and possibly pathogenic LRP10 variant (p.Gly326Asp, p.Asp389Asn, and p.Arg158His, p.Cys220Tyr, p.Thr278Ala, p.Gly306Asp, p.Glu486Asp, p.Arg554∗, p.Arg661Cys). In conclusion, possibly pathogenic LRP10 variants occur in a small fraction of patients with PSP and may be overrepresented in these patients compared with controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.

KW - Genetics

KW - LRP10

KW - Progressive supranuclear palsy

KW - Rare variants

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DO - 10.1016/j.neurobiolaging.2020.04.016

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AN - SCOPUS:85086128224

SN - 0197-4580

VL - 94

SP - 311.e5-311.e10

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

LRP10 variants in progressive supranuclear palsy

Abstract

Keywords

ASJC Scopus subject areas

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