title: Late onset spinal motor neuronopathy is caused by mutation in CHCHD10.
abstract: OBJECTIVE
  A study was undertaken to identify the responsible gene defect underlying late onset spinal motor neuronopathy (LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048), an autosomal dominant disease mapped to chromosome 22q11.2.
  
  
  METHODS
  The previous genetic linkage approach by microsatellite haplotyping was continued in new families. A whole genome sequencing was performed to find all possibly pathogenic mutations in the linked area. The detected variations were verified by Sanger sequencing.
  
  
  RESULTS
  Six new SMAJ families were identified based on the unique founder haplotype. A critical recombination in 1 family restricted the linked area to 727kb between markers SHGC-106816 and D22S345. In whole genome sequencing a previously unknown mutation c.197G>T p.G66V in CHCHD10 was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families.
  
  
  CONCLUSIONS
  Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems.
authors.affiliation: Neuromuscular Research Center, Tampere University and University Hospital, Tampere.
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.forename: Manu
authors.initials: M
authors.lastname: Jokela
authors.forename: Heidi
authors.initials: H
authors.lastname: Bouquin
authors.forename: Anna Maija
authors.initials: AM
authors.lastname: Saukkonen
authors.forename: Jari
authors.initials: J
authors.lastname: Toivanen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005192:Family Health; D005260:Female; D005387:Finland; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: C554426:CHCHD10 protein, human; D024101:Mitochondrial Proteins