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

Neurobiol Aging. 2020 Oct:94:311.e5-311.e10. doi: 10.1016/j.neurobiolaging.2020.04.016. Epub 2020 Apr 30.

Authors

Leonie J M Vergouw¹, Shamiram Melhem¹, Laura Donker Kaat², Wang Z Chiu¹, Demy J S Kuipers³, Guido Breedveld³, Agnita J W Boon⁴, Li-San Wang⁵, Adam C Naj⁶, Elizabeth Mlynarksi⁷, Laura Cantwell⁷, Marialuisa Quadri³, Owen A Ross⁸, Dennis W Dickson⁸, Gerard D Schellenberg⁹, John C van Swieten¹, Vincenzo Bonifati³, Frank Jan de Jong¹⁰

Affiliations

¹ Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
² Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
³ Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁴ Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵ Penn Neurodegeneration Genomics Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Penn Neurodegeneration Genomics Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Penn Neurodegeneration Genomics Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
⁹ Penn Neurodegeneration Genomics Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: [email protected].

PMID: 32527607
PMCID: PMC8281359
DOI: 10.1016/j.neurobiolaging.2020.04.016

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cohort Studies
Exome Sequencing
Exons
Female
Genetic Variation / genetics*
Humans
LDL-Receptor Related Proteins / genetics*
Male
Middle Aged
Supranuclear Palsy, Progressive / genetics*

Substances

LDL-Receptor Related Proteins
LRP10 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding