Parkinson disease: insights in clinical, genetic and pathological features of monogenic disease subtypes

J Chem Neuroanat. 2011 Oct;42(2):131-41. doi: 10.1016/j.jchemneu.2011.07.003. Epub 2011 Jul 26.

Abstract

In the past 15 years, insights in clinical and genetic characteristics of Parkinson disease (PD) have increased substantially. Sequence or copy number variants in at least six genes (SNCA, LRRK2, PARK2, PINK1, DJ-1 and ATP13A2) have been identified to cause monogenic forms of PD. Routine clinical testing for mutations in these genes is feasible and available, but overlapping phenotypes in monogenic and sporadic PD complicate straightforward diagnostic screening. Primarily, a positive familial history and an early onset age should prompt clinicians to consider genetic testing. Based on a literature review on clinical and neuropathological features of PD patients carrying a pathogenic mutation we propose guidelines for genetic diagnostic testing in clinical practice. However, the absence of disease-modifying therapies and the variable penetrance of most known mutations currently limit the usefulness of genetic diagnostic testing for PD in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Association Studies / methods
  • Genetic Association Studies / standards
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods
  • Genetic Testing / standards*
  • Humans
  • Parkinson Disease / classification
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology*