LRP10 variants in progressive supranuclear palsy,Neurobiology of Aging

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LRP10 variants in progressive supranuclear palsy
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.neurobiolaging.2020.04.016
Leonie J M Vergouw ₁ , Shamiram Melhem ₁ , Laura Donker Kaat ₂ , Wang Z Chiu ₁ , Demy J S Kuipers ₃ , Guido Breedveld ₃ , Agnita J W Boon ₄ , Li-San Wang ₅ , Adam C Naj ₆ , Elizabeth Mlynarksi ₇ , Laura Cantwell ₇ , Marialuisa Quadri ₃ , Owen A Ross ₈ , Dennis W Dickson ₈ , Gerard D Schellenberg ₉ , John C van Swieten ₁ , Vincenzo Bonifati ₃ , Frank Jan de Jong ₁

Affiliation

Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
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.
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
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.
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.
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 Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
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.

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.

中文翻译：

进行性核上性麻痹中的 LRP10 变异

本研究的目的是探索 LRP10 的变异，最近与帕金森病和路易体痴呆相关，是否在 2 个进行性核上性麻痹 (PSP) 患者的大型队列（发现和验证队列）中观察到。总共招募了 950 名 PSP 患者：发现队列中有 246 名 PSP 患者（n = 85 可能 (35%)，n = 128 可能 (52%)，n = 33 确定 (13%)）和 704 名 PSP 患者验证队列中有明确的 PSP。在发现队列中对所有 LRP10 外显子和外显子-内含子边界进行 Sanger 测序，在验证队列中进行全外显子测序。发现队列中的 2 名患者和验证队列中的 8 名患者携带罕见的、杂合的、可能致病的 LRP10 变异（p.Gly326Asp、p.Asp389Asn 和 p.Arg158His，p。Cys220Tyr、p.Thr278Ala、p.Gly306Asp、p.Glu486Asp、p.Arg554*、p.Arg661Cys）。总之，可能致病的 LRP10 变异发生在一小部分 PSP 患者中，并且与对照组相比可能在这些患者中出现过多。这表明可能致病的 LRP10 变异可能在 PSP 的发展中发挥作用。

更新日期：2020-10-01

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