title: Subclinical sensory abnormalities in unaffected PINK1 heterozygotes.
abstract: BACKGROUND
  Mutations in the PINK1 gene, encoding a mitochondrial protein kinase, represent the second cause of autosomal recessive parkinsonism (ARP) after Parkin. While homozygous or compound heterozygous mutations in these genes are unequivocally causative of ARP, the role of single heterozygous mutations is still largely debated. An intriguing hypothesis suggests that these mutations could represent a risk factor to develop parkinsonism, by contributing to nigral cell degeneration. Since the substantia nigra plays an important role in temporal processing of sensory stimuli, as revealed from studies in idiopathic PD, we sought to investigate whether any subclinical sensory abnormalities could be detected in patients with PINK1- related parkinsonism and in unaffected PINK1 heterozygous carriers.
  
  
  METHODS
  We adopted a psychophysical method, the temporal discrimination paradigm, to assess PINK1 homozygous patients, unaffected relatives who were heterozygous carriers of the same mutations and healthy control subjects. Temporal discrimination threshold (TDT) and temporal order judgement (TOJ) for pairs of tactile, visual or visuo-tactile stimuli were measured according to a standardized protocol.
  
  
  RESULTS
  Higher mean tactile and visuo-tactile TDTs and TOJs were detected in PINK1 mutation carriers, including not only homozygous patients but also healthy heterozygotes, compared to control subjects (for all comparisons, p < 0.001).
  
  
  CONCLUSIONS
  In clinically unaffected subjects, the mere presence of a heterozygous PINK1 mutation is sufficient to determine sensory alterations which can be disclosed by a psychophysical task. Deficits in temporal processing might be considered as subclinical signs of alteration at least in PINK1-related parkinsonism.
authors.affiliation: Dept. of Neurological and Vision Sciences, Section of Rehabilitative Neurology, University of Verona, Via Casorati 43, 37131, Verona, Italy. mirta.fiorio@medicina.univr.it
authors.forename: Mirta
authors.initials: M
authors.lastname: Fiorio
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Mattia
authors.initials: M
authors.lastname: Gambarin
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: Tamara
authors.initials: T
authors.lastname: Ialongo
authors.forename: Alberto
authors.initials: A
authors.lastname: Albanese
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pellecchia
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Moretto
authors.forename: Antonio
authors.initials: A
authors.lastname: Fiaschi
authors.forename: Michele
authors.initials: M
authors.lastname: Tinazzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004192:Discrimination, Psychological / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D010775:Photic Stimulation / Q000379:methods; D011494:Protein Kinases / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D055698:Touch Perception / Q000502:physiology; D014796:Visual Perception / Q000502:physiology; D055815:Young Adult; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase