The G2019S LRRK2 mutation in Brazilian patients with Parkinson's disease: phenotype in monozygotic twins.
Mutations in the Leucine-Rich Repeat Kinase 2 gene (LRRK2) are mainly responsible for idiopathic Parkinson's disease (PD) with either a dominant pattern of transmission or a sporadic occurrence due to the reduced penetrance. A majority of LRRK2 kindreds demonstrate an extremely variable age-at-onset in affected members of the same family. The G2019S is the most common LRRK2 mutation, which accounts for 1-5% PD patients in North America, and up to 40% of patients from an isolated Arab population. We assessed the frequency of the G2019S mutation in 83 Brazilian PD patients originally preselected for having an early age-at-onset (<50 years) and/or a positive family history. The mutation was detected in three probands (3.5%). Our clinical findings in these kindreds include the first description of the phenotype in identical twins discordant for handedness (a general phenomenon found in approximately 25% monozygotic twins). However, both twins developed right asymmetric PD. The clinical presentation of twins was strikingly similar including an identical PD onset at age 60. This observation may suggest that genetic factors predominantly determine age-at-onset.
Munhoz
Renato P
RP
Movement Disorders Unit, Neurology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil.
Wakutani
Yosuke
Y
Marras
Connie
C
Teive
Helio A
HA
Raskin
Salmo
S
Werneck
Lineu C
LC
Moreno
Danielle
D
Sato
Christine
C
Lang
Anthony E
AE
Rogaeva
Ekaterina
E
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D004200:Diseases in Twins; D005260:Female; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D014430:Twins, Monozygotic
D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine