Comprehensive sequencing of the LRRK2 gene in patients with familial Parkinson's disease from North Africa

Mov Disord. 2010 Oct 15;25(13):2052-8. doi: 10.1002/mds.23283.

Abstract

The LRRK2 gene is a key player in Parkinson's disease (PD), however prevalence and pathogenicity of LRRK2 variants remain to be investigated in ethnically diverse populations. Herein, we performed comprehensive sequencing of the LRRK2 gene in 92 Tunisian probands with familial PD. We then performed an association study using all identified variants in a series of 167 Lrrk2 p.G2019S-negative patients with sporadic PD and 365 Lrrk2 p.G2019S-negative healthy control subjects, all from the same Arab-Berber ethnicity. We identified one novel coding substitution (p.M2408I) and 24 known coding changes. Only the Lrrk2 p.G2019S mutation segregated with disease within families and was found in 39% of familial probands. None of the variants displayed significant association with risk for sporadic PD, however a trend was observed for Lrrk2 p.Y2189C. The present study underscores the importance of the LRRK2 gene in the Tunisian PD population.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa, Northern / ethnology
  • Aged
  • Aged, 80 and over
  • Exons / genetics
  • Family Health*
  • Female
  • Genotype
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Parkinsonian Disorders / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • Sequence Analysis, DNA*

Substances

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