Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase

• DOI: 10.1073/pnas.0914128107
• Publication Date: 2010-04-06T00:35:31Z
• Authors: John Mitchell; Praveen Paul; Han-Jou Chen; Alex Morris; Miles Payling; Mario Falchi; James Habgood; Stefania Panoutsou; Sabine Winkler; Veronica Tisato; Amin Hajitou; Bradley Smith; Caroline Vance; Christopher Shaw; Nicholas D. Mazar...; Jacqueline de Bel...
• Keywords: Pathogenesis

We report a unique mutation in the D-amino acid oxidase gene (R199W DAO) associated with classical adult onset familial amyotrophic lateral sclerosis (FALS) three generational FALS kindred, after candidate screening 14.52 cM region on chromosome 12q22-23 linked to disease. Neuronal cell lines expressing R199W DAO showed decreased viability and increased ubiquitinated aggregates compared cells wild-type protein. Similarly, lentiviral-mediated expression of primary motor neuron cultures caused TUNEL labeling. This effect was also observed when neurons were cocultured transduced astrocytes R199W, indicating that death induced by this is mediated both autonomous noncell processes. controls level D-serine, which accumulates spinal cord cases sporadic ALS mouse model ALS, abnormality may represent fundamental component pathogenesis.