Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease.

Published

Journal Article

Genealogical investigation of a large Norwegian family (F04) with autosomal dominant parkinsonism has identified 18 affected family members over four generations. Genetic studies have revealed a novel pathogenic LRRK2 mutation c.4309 A>C (p.Asn1437His) that co-segregates with disease manifestation (LOD = 3.15, θ = 0). Affected carriers have an early age at onset (48 ± 7.7 SD years) and are clinically asymmetric and levodopa responsive. The variant was absent in 623 Norwegian control subjects. Further screening of patients from the same population identified one additional affected carrier (1 of 692) with familial parkinsonism who shares the same haplotype. The mutation is located within the Roc domain of the protein and enhances GTP-binding and kinase activity, further implicating these activities as the mechanisms that underlie LRRK2-linked parkinsonism.

Full Text

Duke Authors

Cited Authors

  • Aasly, JO; Vilariño-Güell, C; Dachsel, JC; Webber, PJ; West, AB; Haugarvoll, K; Johansen, KK; Toft, M; Nutt, JG; Payami, H; Kachergus, JM; Lincoln, SJ; Felic, A; Wider, C; Soto-Ortolaza, AI; Cobb, SA; White, LR; Ross, OA; Farrer, MJ

Published Date

  • October 2010

Published In

Volume / Issue

  • 25 / 13

Start / End Page

  • 2156 - 2163

PubMed ID

  • 20669305

Pubmed Central ID

  • 20669305

Electronic International Standard Serial Number (EISSN)

  • 1531-8257

International Standard Serial Number (ISSN)

  • 0885-3185

Digital Object Identifier (DOI)

  • 10.1002/mds.23265

Language

  • eng