Identification of a Novel LRRK2 Mutation, 6055G>A (G2019S), Linked to Autosomal Dominant Parkinsonism in Families from Several European Populations

Reference #:

2004-291

Inventors/Contributors

Matthew J. Farrer, Ph.D., Zbigniew K. Wszolek, M.D.

Description

Autosomal dominant parkinsonism linked to chromosome 12q12 (PARK8) has recently been attributed to pathogenic amino acid substitutions in leucine rich repeat kinase 2 (LRRK2). Addition linkage analysis and sequencing, within multiplex families, has confirmed the PARK8 assignment and identified a novel, heterozygous LRRK2 mutation. A referral sample of 248 patients with Parkinson's disease, consistent with autosomal dominant inheritance, was assessed and seven affected probands (2.8%) were found to carry the heterozygous 6055G>A transition (G2019S). Within these families, LRRK2 G2019S segregates with disease (mLODNPL = 2.10, P=.001); of forty-two additional family members examined, twenty-two have a G2019S substitution, and seven had a diagnosis of Parkinson's disease. The families originate from Norway, the US, Ireland, and Poland, but share an ancient ancestral haplotype, indicative of a common European founder. LRRK2 G2019S accounts for many families with autosomal dominant parkinsonism.

Patent Status

Pending