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 two large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 PSP patients were enrolled: 246 PSP patients (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 eight patients from the validation cohort carried a rare, heterozygous, 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 PSP patients and may be overrepresented in these patients compared to controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.