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.

Genetics, LRP10, Progressive supranuclear palsy, Rare variants
dx.doi.org/10.1016/j.neurobiolaging.2020.04.016, hdl.handle.net/1765/127786
Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology
Erasmus MC: University Medical Center Rotterdam

Vergouw, L.J.M, Melhem, S, Donker Kaat, L, Chiu, W.Z, Kuipers, D, Breedveld, G.J, … De Jong, F.J. (2020). LRP10 variants in progressive supranuclear palsy. Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology. doi:10.1016/j.neurobiolaging.2020.04.016