Juvenile-Onset Parkinsonism as a Result of the First Mutation in the Adenosine Triphosphate Orientation Domain of PINK1

Abstract

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 early-onset 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.