Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal loss in the substantia nigra and other brain areas. Despite the vast majority of cases being sporadic, at least six genes have been identified so far that are responsible for autosomal dominant or recessive forms of parkinsonism. The PARK6 locus was mapped to chromosome 1p36 in a Sicilian consanguineous family with autosomal recessive early-onset parkinsonism, and subsequent linkageanalysis in other two consanguineous families, from central Italy and Spain, allowed mapping of the gene to a 2.8cM region on chromosome 1p35–36. Sequencing analysis of candidate genes within the region led to the identification of homozygous mutations in the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) gene: both Italian families carried the W437X non-sense mutation, while the Spanish family carried the G309D missense change.1,2 PINK1 encodes for a serine–threonine kinase that partly localizes to the mitochondria and has been shown to play a major role in protecting neuronal cells from oxidative stress and cell death, mostly functioning alongside other proteins in maintaining mitochondrial morphology and function.^1,3–5

Since identification in 2004, the PINK1 gene has been screened for mutations in large cohorts of parkinsonian patients with variable ages at onset, family histories, and clinical presentations, and several distinct mutations have been detected. While the identification of biallelic mutations in a patient can be unequivocally associated with the phenotype of autosomal recessive parkinsonism (ARP), the finding of a single heterozygous mutation is still of unclear significance. Although the debate on the possible role of such mutations is still open, an intriguing hypothesis suggests that these mutations could represent risk factors for development of idiopathic PD.

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