Prevalence and clinical features of common LRRK2 mutations in Australians with Parkinson's disease

Mov Disord. 2007 May 15;22(7):982-9. doi: 10.1002/mds.21477.

Abstract

We determined the prevalence of two common leucine-rich repeat kinase 2 (LRRK2) gene mutations in Australian patients with Parkinson's disease (PD). Of 830 affected patients, eight were heterozygous for the G2019S mutation, and two were heterozygous for the R1441H (4,322 G > A) mutation. In addition, one familial patient had a novel A1442P (4,324 G > C) mutation. Haplotype analysis showed that all LRRK2 G2019S-positive individuals carried the common founder haplotype 1 and a putative founder haplotype for the R1441H mutation carriers. Clinically, patients with LRRK2 mutations had typical levodopa responsive Parkinsonism with tremor being the commonest presenting feature. Patients with the G2019S mutation in our series had a similar age of onset of symptoms when compared with patients with other LRRK2 mutations or sporadic PD, although they were more likely to have a family history of PD (2.4% of Australian patients with familial PD and 0.3% of Australian patients with sporadic PD). Our results demonstrate that the G2019S mutation carriers share the same ancestors who migrated to Australia originally from Europe and that other LRRK2 mutations (R1441H and A1442P) can be found in this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Australia / epidemiology
  • Cohort Studies
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Genetic Predisposition to Disease
  • Glycine / genetics
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Mutation*
  • Parkinson Disease / epidemiology*
  • Parkinson Disease / genetics*
  • Prevalence
  • Protein Serine-Threonine Kinases / genetics*
  • Serine / genetics

Substances

  • Serine
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • Glycine