Session Information
Date: Monday, September 23, 2019
Session Title: Genetics
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
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.
To cite this abstract in AMA style:
A. Manini, E. Monfrini, L. Straniero, M. Vizziello, G. Franco, S. Duga, A. Di Fonzo. The role of LRP10 mutations in Parkinson’s Disease and Dementia with Lewy Bodies [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/the-role-of-lrp10-mutations-in-parkinsons-disease-and-dementia-with-lewy-bodies/. Accessed September 7, 2024.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-lrp10-mutations-in-parkinsons-disease-and-dementia-with-lewy-bodies/