Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link between familial and idiopathic PD.
The role of genetics in parkinsonism has been confirmed over the last decade with the identification of genetic variation in seven genes, which are causative in familial forms of the disorder. A number of pathogenic mutations have been identified in the latest gene LRRK2, with a Gly2019Ser amino acid substitution identified in two siblings and one patient with idiopathic Parkinson's disease from Ireland. The clinical features resemble the idiopathic variant with a tremor predominant clinical picture shared by the siblings, slow progression of symptoms, and no observation of cognitive disturbance in all. The family and the sporadic individual were apparently not related and originated from different regions of Ireland, although haplotype analysis does suggest they share a common founder. The influence of the G2019S substitution on protein function and disease phenotype has yet to be fully resolved, but its elucidation will undoubtedly further our understanding of the mechanisms underlying Parkinson's disease.
Gosal
David
D
Department of Neurology, Mater Misericordiae Hospital, Eccles St., Dublin 7, Ireland. davidgosal@hotmail.com
Ross
Owen A
OA
Wiley
Joe
J
Irvine
G Brent
GB
Johnston
Janet A
JA
Toft
Mathias
M
Mata
Ignacio F
IF
Kachergus
Jennifer
J
Hulihan
Mary
M
Taylor
Julie P
JP
Lincoln
Sarah J
SJ
Farrer
Matthew J
MJ
Lynch
Timothy
T
Mark Gibson
J
J
D000328:Adult; D019943:Amino Acid Substitution; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003071:Cognition / Q000502:physiology; D018450:Disease Progression; D007839:Functional Laterality / Q000502:physiology; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D000978:Antiparkinson Agents; D007980:Levodopa; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases