期刊
MOVEMENT DISORDERS
卷 25, 期 13, 页码 2156-2163出版社
WILEY-BLACKWELL
DOI: 10.1002/mds.23265
关键词
LRRK2; Parkinson's disease; genetic; kinase
资金
- NIH Udall Parkinson's Disease Research Center of Excellence
- Michael J. Fox Foundation
- Research Council of Norway
- NIH [R00NS058111, R01NS36960]
- American Parkinson's Disease Association
- Intellectual Property Rights
- Expert Testimony
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 5 3.15, theta = 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. (C) 2010 Movement Disorder Society
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