Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson’s disease

Authors


Márcia Mattos Gonçalves Pimentel, PhD. Serviço de Genética Humana, Departamento de Genética, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier, 524, PHLC – sala 500, Maracanã, Rio de Janeiro 20550-013, Brazil (tel.: +55 21 23340039; fax: +55 21 23340309; e-mail: pimentel@uerj.br).

Abstract

Background and purpose:  Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been associated with Parkinson’s disease (PD), and the majority of the pathogenic variants are located in the ROC and MAPKKK domains.

Methods:  Exons 29–31 and 38–44 (ROC and MAPKKK domains) were sequenced in 204 patients with PD, mostly Brazilian.

Results:  We identified four polymorphisms, a novel silent variant p.R1398R and four substitutions: p.T1410M, p.G2019S, p.Y2189C and the novel variant p.C2139S.

Conclusions:  The most prevalent mutation was the p.G2019S (2.4%). We consider that the p.T1410M and the p.Y2189C variants are probably polymorphisms and that the p.C2139S mutation is potentially pathogenic.

Ancillary