Questioning on the role of D amino acid oxidase in familial amyotrophic lateral sclerosis
Year: 2010
Type: letter
Abstract: Mitchell et al. (1) recently reported a single heterozygous variant (R199W) in exon 7 of D amino oxidase (DAO) gene in a family with amyotrophic lateral sclerosis (ALS) that showed a probable linkage to the 12q chromosome (Zmax of 2.7 for d12s1646 by bipoint and 1.9 for d12S330 by multipoint analysis) (1). Characteristics of this variant were in favor of its causative role in this family: it was found in three affected members and one obligate carrier, it was absent in 780 controls matched for ethnic background, and it was relatively well-conserved among species. Moreover, cellular studies performed with lentiviral vectors expressing mutant or wild-type DAO protein showed that R199W DAO led to ubiquitin aggregate formation and decreased cellular viability in vitro. Overall, the identification of a second rare variant in another familial amyotrophic lateral sclerosis (FALS) would be of great interest to firmly incriminate DAO in ALS. In an effort to strengthen these data, we sequenced the 10 coding exons (exons 2–11) of DAO and exon–intron junctions (Ensembl reference sequence ENS0110887) in 126 unrelated patients living in France presenting probable or definite ALS with at least one ALS-affected relative. Spinal and bulbar onset was noticed in 80.2% and 29.8% of these patients, respectively. The mean disease onset was 58 ± 9 y, and the mean disease duration was 3 ± 2 y. Protocols were approved by the Medical Research Ethics Committee of Assistance Publique-Hopitaux de Paris. All participants signed a consent form for the research. Mutations in copper/zinc superoxide dismutase (SOD1), angiogenin (ANG), vesicle associated membrane protein associated protein B (VAPB), TAR DNA binding protein 43 (TARDBP), and fused in sarcoma (FUS) have been excluded in these patients (2).
Institutions: Centre National de la Recherche Scientifique, Inserm, Pitié-Salpêtrière Hospital, Institut du Cerveau, Université Pierre-et-Marie-Curie, Assistance Publique – Hôpitaux de Paris, Centre Hospitalier Universitaire de Lille, Hôpital Roger Salengro, Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Hôpital Gui de Chauliac, Université Montpellier 1
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2043713952