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

Clinical Neurology
Geriatrics and Gerontology
Aging
General Neuroscience
Developmental Biology

Access to Document

10.1016/j.neurobiolaging.2020.04.016

Cite this

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 = "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

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

UR - http://www.scopus.com/inward/record.url?scp=85086128224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85086128224&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2020.04.016

DO - 10.1016/j.neurobiolaging.2020.04.016

M3 - Article

C2 - 32527607

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

Access to Document

Other files and links

Fingerprint

Cite this