title: Identification of p.Gln858* in ATP13A2 in two EOPD patients and presentation of their clinical features.
abstract: We present results of homozygosity mapping in two siblings affected with early onset Parkinson's disease (EOPD) and mutation screening of ATP13A2 in these and other Iranian EOPD patients. Genome-wide SNP homozygosity analysis revealed linkage to a locus that included ATP13A2, and sequencing of the gene revealed a novel p.Gln858*-causing mutation in the homozygous state in the siblings. Sequencing of the gene in seven other unrelated EOPD patients previously shown not to have mutations in PRKN, DJ-1, PINK1, and LRRK2 identified the same homozygous p. Gln858*-causing mutation in another patient. Haplotype analysis revealed that two alleles harboring the mutation were not identical by decent. The variation identified represents the 13th known disease causing mutation in ATP13A2. The clinical features of the patients who harbored the mutation are compared to those of previously reported patients with mutations in ATP13A2. Bradykinesia and rigidity, but not tremor, were reported in nearly all the patients. l-dopa administration, though initially effective, usually caused dyskinesia upon prolonged usage. Eye movement abnormalities including saccades and supranuclear gaze palsy, were almost always observed. Dystonia and bulbar anomalies were common but more variable manifestations. Although a degree of cognitive decline was found in most of the patients, the decline was often mild and absent in one patient. Age at onset of symptoms was usually in the second decade of life, and sometimes in the third decade.
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Malakouti-Nejad
authors.affiliation: Department of Neurology, HazratRasool Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Gholam-Ali
authors.initials: GA
authors.lastname: Shahidi
authors.affiliation: Department of Neurology, HazratRasool Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rohani
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Seyed Mehdi
authors.initials: SM
authors.lastname: Shojaee
authors.affiliation: Department of Genetics, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.affiliation: Illumina, San Diego, CA, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran; School of Biology, College of Science, University of Tehran, Tehran, Iran. Electronic address: elaheelahi@ut.ac.ir.
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D005260:Female; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D006180:Proton-Translocating ATPases / Q000235:genetics*; D055815:Young Adult
chemical_list: C514983:ATP13A2 protein, human; D006180:Proton-Translocating ATPases
keywords: ATP13A2; EOPD; Early onset Parkinson's disease; Homozygosity mapping; p.Gln858*