Juvenile-onset parkinsonism as a result of the first mutation in the adenosine triphosphate orientation domain of PINK1

Background: Mutations in the PTEN-induced putative kinase 1 (PINK1) gene at 1p36 have been involved in autosomal recessive early-onset parkinsonism. Objective: To describe the clinical and genetic features of the largest kindred reported to date with earlyonset parkinsonism associated with the PINK1 gene. Design: Clinical and genetic study. Setting: Collaborative study. Patients: Eight patients from Sudan with particularly early onset (ages 9-17 years) and phenotypes varying from dopa-responsive dystonia-like to typical early-onset parkinsonism. Main Outcome Measures: The PINK1 genotype and Parkinson disease status of all available family members. Results: The disease was caused by a novel mutation, p.A217D, located in the highly conserved adenosine triphosphate orientation site of the PINK1 kinase domain. Conclusion: This study extends the phenotypic and molecular spectrum of the PINK1 gene and the geographic origin of patients with PINK1 gene mutations. ©2006 American Medical Association. All rights reserved.