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Subclinical sensory abnormalities in unaffected PINK1 heterozygotes

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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.

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Authors and Affiliations

  1. Dept. of Neurological and Vision Sciences, Section of Rehabilitative Neurology, University of Verona, Via Casorati 43, 37131, Verona, Italy

    M. Fiorio PhD, M. Gambarin MD, A. Fiaschi MD & M. Tinazzi MD

  2. IRCCS CSS, Mendel Institute, Viale Regina Margherita 26, 00198, Rome, Italy

    E. M. Valente MD & F. Brancati MD

  3. Operative Unit of Pediatric Genetics and Immunology, Dept. of Medical and Surgical Pediatric Sciences, University of Messina, Viale Gazzi, 98100, Messina, Italy

    E. M. Valente MD

  4. Institute of Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy

    A. R. Bentivoglio MD & T. Ialongo MD

  5. IRCCS National Neurological Institute, Carlo Besta, Via Celoria 11, 20133, Milan, Italy

    A. Albanese MD

  6. Dept. of Neurological Sciences, University Federico II, Corso Umberto I, 80138, Naples, Italy

    P. Barone MD & M. T. Pellecchia MD

  7. CeSI, Aging Research Centre and Dept. of Biomedical Sciences, G. d’Annunzio University Foundation, Via dei Vestini 31, 66013, Chieti, Italy

    F. Brancati MD

  8. Neurology Unit, Borgo Trento Hospital, Piazzale Stefani 1, 37100, Verona, Italy

    G. Moretto MD & M. Tinazzi MD

Authors
  1. M. Fiorio PhD
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  2. E. M. Valente MD
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  3. M. Gambarin MD
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  4. A. R. Bentivoglio MD
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  5. T. Ialongo MD
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  6. A. Albanese MD
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  7. P. Barone MD
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  8. M. T. Pellecchia MD
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  9. F. Brancati MD
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  10. G. Moretto MD
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  11. A. Fiaschi MD
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  12. M. Tinazzi MD
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Corresponding author

Correspondence to M. Fiorio PhD.

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Fiorio, M., Valente, E.M., Gambarin, M. et al. Subclinical sensory abnormalities in unaffected PINK1 heterozygotes. J Neurol 255, 1372–1377 (2008). https://doi.org/10.1007/s00415-008-0923-6

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  • DOI: https://doi.org/10.1007/s00415-008-0923-6

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