title: Genetic overlap between apparently sporadic motor neuron diseases.
abstract: Progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) are devastating motor neuron diseases (MNDs), which result in muscle weakness and/or spasticity. We compared mutation frequencies in genes known to be associated with MNDs between patients with apparently sporadic PMA and ALS. A total of 261 patients with adult-onset sporadic PMA, patients with sporadic ALS, and control subjects of Dutch descent were obtained at national referral centers for neuromuscular diseases in The Netherlands. Sanger sequencing was used to screen these subjects for mutations in the coding regions of superoxide dismutase-1 (SOD1), angiogenin (ANG), fused in sarcoma/translated in liposarcoma (FUS/TLS), TAR DNA-binding protein 43 (TARDBP), and multivesicular body protein 2B (CHMP2B). In our cohort of PMA patients we identified two SOD1 mutations (p.D90A, p.I113T), one ANG mutation (p.K17I), one FUS/TLS mutation (p.R521H), one TARDBP mutation (p.N352S), and one novel CHMP2B mutation (p.R69Q). The mutation frequency of these genes was similar in sporadic PMA (2.7%) and ALS (2.0%) patients, and therefore, our findings demonstrate a genetic overlap between apparently sporadic PMA and ALS.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marka
authors.initials: M
authors.lastname: van Blitterswijk
authors.forename: Lotte
authors.initials: L
authors.lastname: Vlam
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: W-Ludo
authors.initials: WL
authors.lastname: van der Pol
authors.forename: Eric A M
authors.initials: EA
authors.lastname: Hennekam
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.forename: Helenius J
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation; D034702:RNA-Binding Protein FUS / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C503812:CHMP2B protein, human; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C046366:angiogenin; D012259:Ribonuclease, Pancreatic