title: Hereditary motor neuron disease in a large Norwegian family with a "H46R" substitution in the superoxide dismutase 1 gene.
abstract: Mutant genes associated with Charcot Marie Tooth type 2, distal hereditary motor neuropathy and familial amyotrophic lateral sclerosis may cause overlapping clinical phenotypes. We performed whole genome linkage analysis, haplotype analysis, sequencing and detailed clinical and neurophysiological investigations in a large Norwegian kindred with a condition that clinically had been classified as Charcot Marie Tooth type 2. The mutation c.140A>G, p.His47Arg (alias p.His46Arg or H46R) in the superoxide dismutase 1 gene (SOD1) segregated with the disease. The patients present a hereditary motor neuropathy-like clinical picture and long survival (mean 29years). To our knowledge, this is the first extensive report describing a large non-Japanese kindred. The prognostic implications of the condition seen in this family have little in common with what is normally associated with sporadic amyotrophic lateral sclerosis and illustrates the complexity of the genetic etiology of lower motor neuron disease.
authors.affiliation: Department of Clinical Medicine - Medical Genetics, University of Tromsø, NO9037 Tromsø, Norway. Rune.Andre.Helland.Ostern@unn.no
authors.forename: Rune
authors.initials: R
authors.lastname: Østern
authors.forename: Toril
authors.initials: T
authors.lastname: Fagerheim
authors.forename: Kristin
authors.initials: K
authors.lastname: Ørstavik
authors.forename: Trygve
authors.initials: T
authors.lastname: Holmøy
authors.forename: Arvid
authors.initials: A
authors.lastname: Heiberg
authors.forename: Inger
authors.initials: I
authors.lastname: Lund-Petersen
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Nilssen
authors.forename: Arve
authors.initials: A
authors.lastname: Dahl
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics*; D009154:Mutation; D009431:Neural Conduction; D009664:Norway; D010375:Pedigree; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1