The LRRK2 G2019S mutation as the cause of Parkinson's disease in Ashkenazi Jews.
Mutations in the leucine rich repeat kinase 2 gene (LRRK2) are recognized as the most common cause of genetic Parkinsonism to date. The G2019S mutation has been implicated as an important determinant of Parkinson's disease (PD) in both Ashkenazi Jewish and North African Arab populations with carrier frequency of 29.7% among familial and 6% in sporadic Ashkenazi Jewish PD cases. PD patients with the G2019S mutation display similar clinical characteristics to patients with sporadic PD. While the function of the LRRK2 protein has yet to be fully determined, its distribution coincides with brain areas most affected by PD. The G2019S mutation is believed to be responsible for up-regulation of LRRK2 kinase activity, which may ultimately play a role in neuronal loss. The utility of LRRK2 G2019S screening in family members of Ashkenazi PD patients is discussed. LRRK2 G2019S mutation carriers without PD may be an ideal population for the study of possible neuroprotective strategies as they become available, and for furthering the understanding of the pathogenesis and long-term clinical outcomes of the disease.
Thaler
Avner
A
Department of Neurology, Sourasky Medical Center, Tel-Aviv, Israel. avnerth@gmail.com
Ash
Elissa
E
Gan-Or
Ziv
Z
Orr-Urtreger
Avi
A
Giladi
Nir
N
D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005820:Genetic Testing / Q000592:standards; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000208:ethnology / Q000235:genetics*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases