PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum. Academic Article uri icon

Overview

abstract

  • Heterozygous rare variants in the PINK1 gene, as well as in other genes causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare variants in over 1100 sporadic and familial patients of all onset ages and in 400 controls. Twenty patients and 6 controls were heterozygous, with frequencies (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features of heterozygotes were indistinguishable to those of wild-type patients, with mean disease onset 10 years later than in carriers of two mutations but worse disease progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk is only slightly increased with a non significant odds ratio of 1.62. These findings suggest that PINK1 heterozygous rare variants play only a minor susceptibility role in the context of a multifactorial model of PD. Hence, their significance should be kept distinct from that of homozygous/compound heterozygous mutations, that cause parkinsonism inherited in a mendelian fashion.

authors

  • Marongiu, Roberta
  • Ferraris, Alessandro
  • Ialongo, Tàmara
  • Michiorri, Silvia
  • Soleti, Francesco
  • Ferrari, Francesca
  • Elia, Antonio E
  • Ghezzi, Daniele
  • Albanese, Alberto
  • Altavista, Maria Concetta
  • Antonini, Angelo
  • Barone, Paolo
  • Brusa, Livia
  • Cortelli, Pietro
  • Martinelli, Paolo
  • Pellecchia, Maria Teresa
  • Pezzoli, Gianni
  • Scaglione, Cesa
  • Stanzione, Paolo
  • Tinazzi, Michele
  • Zecchinelli, Anna
  • Zeviani, Massimo
  • Cassetta, Emanuele
  • Garavaglia, Barbara
  • Dallapiccola, Bruno
  • Bentivoglio, Anna Rita
  • Valente, Enza Maria

publication date

  • April 1, 2008

Research

keywords

  • Genetic Variation
  • Parkinson Disease
  • Protein Kinases

Identity

Scopus Document Identifier

  • 42049102405

Digital Object Identifier (DOI)

  • 10.1002/humu.20719

PubMed ID

  • 18330912

Additional Document Info

volume

  • 29

issue

  • 4