Identification of VPS35 mutations replicated in French families with Parkinson disease

Since Next Generation DNA Sequencing (NGS) was first used to study Miller syndrome,1 exome capture and sequencing have uncovered novel causative mutations in an increasing number of genetic disorders, including neurodegenerative diseases.2–4 Two independent groups recently found the same heterozygous missense mutation, D620N (c.1858G>A), in the vacuolar protein sorting 35 ortholog gene ( VPS35 ) associated with autosomal dominant late-onset Parkinson disease (PD).5,6 It segregated with the disease in 2 large families of Swiss5 and Austrian origin.6 Further screening by both groups detected the mutation in 8 families from Austria, Switzerland, the United States, Tunisia, and Israel, and 2 rare, potentially pathogenic variants (P316S, R524W) in 1 family in each of the studies. We screened the VPS35 gene in a large sample of PD families with autosomal dominant inheritance, mostly from France, and analyzed the associated phenotypes.