title: Variability in clinical phenotypes of heterozygous and homozygous cases of Parkin-related Parkinson's disease.
abstract: Parkin mutations are a common cause of early-onset Parkinson's disease. To study the clinical features and treatment responses of patients with homozygous or heterozygous Parkin mutations, we performed a retrospective chart review in six early-onset parkinsonism patients with pathogenic Parkin mutations. The clinical phenotypes observed in this cohort, all drawn from different families, were variable. All patients had a slowly progressive form of parkinsonism that responded well to dopaminergic therapy with the exception of one advanced case. Homozygous patients had an earlier age at disease onset than heterozygous patients. Two of our patients underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus leading to a sustained positive response. Our observations support an earlier age of onset for homozygous cases and possible beneficial effects of DBS in Parkin-related parkinsonism.
authors.affiliation: 1Departments of Neurology and Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida , Gainesville, FL , USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Angela
authors.initials: A
authors.lastname: Hardwick
authors.forename: Nikolaus R
authors.initials: NR
authors.lastname: McFarland
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
mesh_terms: D000368:Aged; D046690:Deep Brain Stimulation; D015259:Dopamine Agents; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005917:Globus Pallidus / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000628:therapy; D010641:Phenotype; D012189:Retrospective Studies; D020531:Subthalamic Nucleus / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D015259:Dopamine Agents; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein