Subclinical sensory abnormalities in unaffected PINK1 heterozygotes

M. Fiorio, E. M. Valente, M. Gambarin, A. R. Bentivoglio, T. Ialongo, A. Albanese, P. Barone, M. T. Pellecchia, F. Brancati, G. Moretto, A. Fiaschi, M. Tinazzi

Research output: Contribution to journalArticle

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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. Findings: 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). Interpretation: 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.

Original languageEnglish
Pages (from-to)1372-1377
Number of pages6
JournalJournal of Neurology
Volume255
Issue number9
DOIs
Publication statusPublished - Sep 2008

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Heterozygote
Parkinsonian Disorders
Touch
Mutation
Substantia Nigra
Mitochondrial Proteins
Protein Kinases
Genes
Healthy Volunteers

Keywords

  • Endophenotype
  • Parkinson's disease
  • PINK1
  • Sensory systems
  • Temporal discrimination

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Fiorio, M., Valente, E. M., Gambarin, M., Bentivoglio, A. R., Ialongo, T., Albanese, A., ... Tinazzi, M. (2008). Subclinical sensory abnormalities in unaffected PINK1 heterozygotes. Journal of Neurology, 255(9), 1372-1377. https://doi.org/10.1007/s00415-008-0923-6

Subclinical sensory abnormalities in unaffected PINK1 heterozygotes. / Fiorio, M.; Valente, E. M.; Gambarin, M.; Bentivoglio, A. R.; Ialongo, T.; Albanese, A.; Barone, P.; Pellecchia, M. T.; Brancati, F.; Moretto, G.; Fiaschi, A.; Tinazzi, M.

In: Journal of Neurology, Vol. 255, No. 9, 09.2008, p. 1372-1377.

Research output: Contribution to journalArticle

Fiorio, M, Valente, EM, Gambarin, M, Bentivoglio, AR, Ialongo, T, Albanese, A, Barone, P, Pellecchia, MT, Brancati, F, Moretto, G, Fiaschi, A & Tinazzi, M 2008, 'Subclinical sensory abnormalities in unaffected PINK1 heterozygotes', Journal of Neurology, vol. 255, no. 9, pp. 1372-1377. https://doi.org/10.1007/s00415-008-0923-6
Fiorio M, Valente EM, Gambarin M, Bentivoglio AR, Ialongo T, Albanese A et al. Subclinical sensory abnormalities in unaffected PINK1 heterozygotes. Journal of Neurology. 2008 Sep;255(9):1372-1377. https://doi.org/10.1007/s00415-008-0923-6
Fiorio, M. ; Valente, E. M. ; Gambarin, M. ; Bentivoglio, A. R. ; Ialongo, T. ; Albanese, A. ; Barone, P. ; Pellecchia, M. T. ; Brancati, F. ; Moretto, G. ; Fiaschi, A. ; Tinazzi, M. / Subclinical sensory abnormalities in unaffected PINK1 heterozygotes. In: Journal of Neurology. 2008 ; Vol. 255, No. 9. pp. 1372-1377.
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AU - Barone, P.

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AB - 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. Findings: 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). Interpretation: 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.

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