LRP10 variants in progressive supranuclear palsy.

Autor: Vergouw LJM; Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Melhem S; Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Donker Kaat L; 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., Chiu WZ; Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Kuipers DJS; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Breedveld G; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Boon AJW; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Wang LS; 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., Naj AC; 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., Mlynarksi E; 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., Cantwell L; 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., Quadri M; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Ross OA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA., Dickson DW; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA., Schellenberg GD; 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., van Swieten JC; Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Bonifati V; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., de Jong FJ; Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: f.j.dejong@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2020 Oct; Vol. 94, pp. 311.e5-311.e10. Date of Electronic Publication: 2020 Apr 30.
DOI: 10.1016/j.neurobiolaging.2020.04.016
Abstrakt: 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.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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