Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Genetics, Islamic Azad University, Tehran Medical Branch, Tehran, Iran.
Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
School of Biology, University College of Science, University of Tehran, Iran.; Department of Biotechnology, University College of Science, University of Tehran, Iran.
Parkinson’s disease (PD) is a prevalent neurodegenerative disease that usually affects individuals over 50 years of age. Age at onset in a small subset of PD cases is considerably lower, and these are considered early-onset PD (EOPD) patients. Most PD cases appear sporadic, but approximately 15% are familial, and some of the familial cases exhibit Mendelian inheritance. Genetic analysis of familial cases has led to identification of five major PD causing genes. Mutations in three of these, PRKN, PINK1, and DJ-1 are most often observed in EOPD patients belonging to families in which PD is inherited in an autosomal recessive fashion. Here, a PD family with two siblings whose ages of onset were 10 and 14 years was identified. Initially, PRKN, PINK1, and DJ-1 were screened, but a putative disease causing mutation was not found. Genome-wide homozygosity mapping using high density microarray chips led to identification of a 6.5 cM linked locus on locus on chromosome 1. ATP13A2 that encodes a lysosomal type 5 P-type ATPase is positioned within the linked locus. Mutations in ATP13A2 have previously been reported in a few EOPD patients, and this gene is an appropriate candidate as cause of PD in the pedigree here described.