Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism

Ann Neurol. 2004 Sep;56(3):427-31. doi: 10.1002/ana.20247.

Abstract

Two homozygous mutations in the PINK1 gene, encoding a mitochondrial putative protein kinase, recently have been identified in families with PARK6-linked, autosomal recessive early-onset parkinsonism (AREP). Here, we describe a novel homozygous mutation (1573_1574 insTTAG) identified in an AREP patient, which causes a frameshift and truncation at the C-terminus of the PINK1 protein, outside the kinase catalytic domain. The clinical phenotype includes early-onset (28 years) parkinsonism, foot dystonia at onset, good levodopa response, slow progression, early levodopa-induced dyskinesias, and sleep benefit, thereby resembling closely parkin-related disease. These findings confirm that recessive mutations in PINK1 cause early-onset parkinsonism and expand the associated clinical phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Amino Acid Sequence
  • Female
  • Homozygote*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Parkinsonian Disorders / enzymology*
  • Parkinsonian Disorders / genetics*
  • Pedigree
  • Peptide Fragments / genetics*
  • Protein Kinases / genetics*

Substances

  • Peptide Fragments
  • Protein Kinases
  • PTEN-induced putative kinase