title: Investigation of the role of SMN1 and SMN2 haploinsufficiency as a risk factor for Hirayama's disease: clinical, neurophysiological and genetic characteristics in a Spanish series of 13 patients.
abstract: OBJECTIVE
  The effect of the number of copies in the SMN1 and SMN2 genes - the most extensively studied susceptibility and modifying genetic factors in adult onset motor neuron diseases - as a genetic risk factor for Hirayama's disease (HirD) has never been studied. The purpose of this study was to investigate the influence of the number of copies of the SMN1/SMN2 genes on the resulting phenotype in 13 HirD Spanish patients.
  
  
  METHODS
  We performed a qualitative and quantitative SMN1/SMN2 gene analysis in 13 unrelated HirD patients. The phenotype-genotype correlation was investigated, paying particular attention to the effect of the SMN1/SMN2 copy number on the disease's phenotype.
  
  
  RESULTS
  No patient had a homozygous deletion of the SMN1 or SMN2. No differences were found when comparing the SMN1 and SMN2 copy number distributions of the healthy population and HirD patients, and they do not therefore appear to be a susceptibility factor. There was also no correlation found between the number of copies of the SMN1 and SMN2 and the severity of the resulting phenotype.
  
  
  CONCLUSIONS
  Our results suggest that SMN1 and SMN2 are not predisposing factors for HirD and therefore support a lack of association between these genes and the resulting phenotype.
authors.affiliation: Department of Neurology, Hospital Gral. Vall d'Hebron, UAB, Passeig Vall d'Hebron 119-135, 08035 Barcelona, Spain. 12784jgc@comb.es
authors.forename: Josep
authors.initials: J
authors.lastname: Gamez
authors.forename: Eva
authors.initials: E
authors.lastname: Also
authors.forename: Laura
authors.initials: L
authors.lastname: Alias
authors.forename: Marc
authors.initials: M
authors.lastname: Corbera-Bellalta
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Barceló
authors.forename: Maria
authors.initials: M
authors.lastname: Centeno
authors.forename: Nuria
authors.initials: N
authors.lastname: Raguer
authors.forename: Margarita
authors.initials: M
authors.lastname: Gratacós
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
mesh_terms: D000328:Adult; D001284:Atrophy; D002470:Cell Survival / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004576:Electromyography; D005260:Female; D005542:Forearm / Q000294:innervation*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005828:Genetics, Population; D006225:Hand / Q000294:innervation*; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016472:Motor Neuron Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009046:Motor Neurons / Q000502:physiology; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009460:Neurologic Examination; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D013030:Spain; D013116:Spinal Cord / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D013577:Syndrome
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein