ABSTRACT
PINK1 (PTEN-induced kinase 1) is the third gene to be associated with autosomal recessive Parkinson’s disease (ARPD) following PARKIN and DJ-1. Mutations in PINK1 were identified in three consanguineous families from Italy and Spain. Subsequent mutation screens from several groups around the world reported PINK1 mutations in ARPD at a frequency between those in PARKIN, which account for approximately 50% of cases under 50 years old, and DJ-1, which remain quite rare at approximately 1%. Clinically, PINK1-positive patients present with a phenotype which is remarkably similar to idiopathic Parkinson’s disease (PD), albeit with a younger age at onset and slower progression. Pathologic data from PINK1 heterozygote cases have demonstrated the presence of Lewy bodies, eosinophilic cytoplasmic inclusions that are the pathologic hallmark of idiopathic PD. It remains to be determined if homozygote mutants also develop Lewy bodies or are more similar to PARKIN cases, where loss of dopaminergic neurons can occur independently of Lewy body formation.
