Background: PARK4 is a candidate locus for familial Parkinson's disease (PD), combined with multiplication of the α-synuclein gene (SNCA). The eventual phenotype is dependent on the copy number of SNCA. Mutations in leucine-rich repeat kinase 2 (LRRK2) are also causative of parkinsonism. This report describes a man who presented at our hospital complaining of a stagger after running and difficulty in handling the mouse of a personal computer, having suffered tremors since his twenties. Nine months after treatment and discharge, he developed titubation and began to drag his right foot.
Methods: We examined the patient's family pedigree for SNCA dosage, using quantitative polymerase chain reaction. We also screened this pedigree for mutations in parkin and LRRK2, using gene-sequencing techniques.
Results: We identified the proband, his sister, and his paternal uncle as carrying a duplication of SNCA. In addition, we found that the proband and his mother carried the G2385R variant of the LRRK2, a strong risk factor for PD in Asians and the rare V1450I variant, although only the proband showed symptoms of parkinsonism. No mutations were found in parkin.
Conclusions: The combination of SNCA gene duplication and LRRK2 G2385R variant may explain the early onset of disease in this patient.
Copyright © 2012 Movement Disorders Society.