Objective: To test LRP10 in a cohort of Italian patients, with a clinical diagnosis of either Parkinson’s Disease (PD) (n=316) or Dementia with Lewy Bodies (DLB) (n=10).

Background: PD and DLB belong to a continuum spectrum of neurodegenerative diseases characterized by alpha-synuclein accumulation in neurons. Even though alpha-synucleinopathies pathogenesis remains largely uncovered, the development of novel techniques in the field of genetics has brought to the discovery of at least 23 loci and 19 disease-causing genes for parkinsonism. Recently, a new candidate gene (LRP10) for PD and DLB has been identified by performing a linkage analysis and positional cloning on a large Italian family with late-onset PD. After the first characterization of a LRP10 pathogenic mutation, other eight variants have been detected in an international multicenter series of 660 probands with either a clinical or pathological diagnosis of PD or DLB.

Method: A genetic analysis of LRP10 was assessed by Sanger sequencing in 176 patients affected by PD and 10 by DLB. A second cohort of 140 PD cases was analysed by NGS panel approach. LRP10 variants identified were subsequently confirmed by Sanger sequencing.

Results: Six variants (MAF<1%) were identified in a total of ten patients: one was synonymous (c. 1923G>A) and one was detected in an intronic region (c. 80-23G>A); four (c. 415A>G, c. 1646G>A, c. 1685G>A and c. 1991C>T) led to a missense change at protein level, respectively p. M139V, p. R549Q, p. R562H and p. R661C. The c. 1923G>A was predicted to generate a potential splice site change.

Conclusion: In conclusion, several LRP10 rare variants were detected in patients with Parkinson’s Disease. Further investigations will be employed to define the precise role of these variants in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-lrp10-mutations-in-parkinsons-disease-and-dementia-with-lewy-bodies/