The enigmatic link between glucocerebrosidase and parkinsonism: New pieces to the puzzle

✍ Scribed by Grisel Lopez; Ellen Sidransky

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 45 KB
• Volume: 26
• Category: Article
• ISSN: 0885-3185
• DOI: 10.1002/mds.23923

✦ Synopsis

The identification of genetic mutations that cause Parkinson's disease (PD) in rare families has been the bedrock of investigation into the molecular pathogenesis of PD. These mutations are used to understand and model disease in a process aimed at finding viable points of therapeutic intervention based on etiology, rather than being based on symptomatic relief.

Two articles published back to back in the American Journal of Human Genetics expand the repertoire of genetic tools with which to understand the basis of PD by the discovery of a mutation linked to PD in the VPS35 gene. Both studies used exome sequencing, a method to sequence all the protein-coding regions of the genome in parallel, in large families with PD. In the work by Vilarin ˜o-Gu ¨ell and colleagues, the authors sequenced cousins from a large Swiss kindred with autosomal-dominant late-onset PD. Following a series of screening and filtering steps, the authors provide evidence that a mutation in VPS35 (p.D620N) is responsible for disease in this family and in 4 of approximately 4000 unrelated PD cases screened. The mutation was absent from more than 3000 control samples. In the work by Zimprich and col-