Familial early onset Parkinson's disease caused by a homozygous frameshift variant in PARK7: Clinical features and literature update

Abstract

BackgroundBi-allelic mutations in PARK7 are a rare cause of autosomal recessive early onset Parkinson's disease (EO-PD). To date, 30 individuals harbouring 20 unique causative variants have been described. Understanding of the spectrum of clinical features and natural history of PARK7 mediated EO-PD remain limited. MethodsWe studied a family with three offspring, two of whom were affected with EO-PD. Family members underwent detailed clinical examination and DNA samples from both affected individuals and parents were analysed by exome sequencing. ResultsTwo brothers of Iranian descent presented at age 29 years with Parkinsonism associated with high-pitched voice and hypomimia. The brothers were followed over a six and fifteen-year period and displayed typical levodopa responsive slowly-progressive Parkinsonism. A novel homozygous frameshift mutation in PARK7 [NM_007262.4:c.90dupG, p(Ile31Aspfs*2)] was identified. ConclusionsHere we report the clinical presentation and progression of EO-PD in brothers with a novel pathogenic PARK7 variant. We expand the clinical phenotype and provide an update of clinical and pathological features of the disorder.