Early-onset Parkinson's disease due to PINK1 p.Q456X mutation--clinical and functional study.

ABSTRACT:

Background

Recessive mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause early-onset Parkinson's disease (EOPD). The clinical phenotype of families that have this PINK1-associated disease may present with different symptoms, including typical PD. The loss of the PINK1 protein may lead to mitochondrial dysfunction, which causes dopaminergic neuron death.

Methods

The clinical phenotypes of a large Polish family with EOPD and an identified PINK1 homozygous nonsense mutation were assessed. Ubiquitination and degradation of mitochondrial parkin substrates as well as mitochondrial bioenergetics were investigated as direct functional readouts for PINK1's kinase activity in biopsied dermal fibroblasts.

Results

A four-generation family was genealogically evaluat

SUBMITTER: Siuda J 

PROVIDER: S-EPMC4253017 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature