LRP10 variants in Parkinson's disease and dementia with Lewy bodies in the South-West of the Netherlands

Abstract

Objective: To analyse LRP10 variants, recently associated with the development of Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), in a series of patients and controls from the South-West of the Netherlands (Walcheren).

Methods: A series of 130 patients with PD, PDD or DLB were clinically examined, and a structured questionnaire used to collect information about family history of PD and dementia. The entire LRP10 coding region was sequenced by Sanger methods in all patients, and haplotype analysis was performed for one recurrent LRP10 variant. The fragments containing possibly pathogenic LRP10 variants were sequenced in 62 unaffected control subjects from the same region. Other known PD-associated genes were analyzed by exome sequencing and gene dosage in the carriers of LRP10 variants.

Results: Four patients were carriers of a rare heterozygous, possibly pathogenic LRP10 variant: p.Arg151Cys, p.Arg263His, and p.Tyr307Asn. None of these variants was detected among the controls, nor were additional mutations identified in known PD-associated genes in the four LRP10 variant carriers. The previously reported p.Tyr307Asn variant was identified in two patients (with PD and PDD), who are connected genealogically within six generations, and in one of their relatives with cognitive decline. Haplotype analysis suggests a common founder for the p.Tyr307Asn variant carriers analyzed.

Discussion: We report three possibly pathogenic LRP10 variants in patients with PD and PDD from a local Dutch population. The identification of additional patients carrying the p.Tyr307Asn variant provides some further evidence that this variant is pathogenic for PD and PDD.

Keywords: Dementia with Lewy bodies; LRP10 gene; Parkinson's disease; Parkinson's disease dementia; Walcheren population.