title: Association between centromeric deletions of the SMN gene and sporadic adult-onset lower motor neuron disease.
abstract: The telomeric copy (t) of the survival motor neuron (SMN) gene is homozygously deleted in more than 90% of patients with infantile motor neuron disease (MND). In the general population, no homozygous SMNt deletion has been found, whereas 5% of centromeric SMN (SMNc) deletions can be observed. Although SMNt deletions appear causal for infantile and at least some adult-onset spinal muscular atrophy (SMA) (type IV), the respective role of SMN deletions remains unclear in adult-onset MNDs. We studied SMN gene in three different groups of patients with adult-onset MNDs. In sporadic amyotrophic lateral sclerosis (ALS; n = 177) and familial ALS (n = 66), no SMNt deletion had been found, and the frequency of SMNc deletions was not increased. Conversely, among the 14 patients with sporadic pure lower MND (LMND), we found 2 patients with homozygous SMNt deletions (14%) and 5 patients with homozygous SMNc deletions (36%). These data suggest that (1) SMNt deletions do not account for the major part, if any, of adult-onset LMND cases; and (2) SMNc deletions act as a susceptibility factor for LMNDs in adults. The clinical and genetic heterogeneity of LMND cases, including SMA type IV, are yet to be unexplained. Further studies on large groups of adult-onset LMND patients are warranted to refine its nosology.
authors.affiliation: Laboratoire de Médecine Expérimentale, Institut de Biologie, Montpellier, France.
authors.forename: B
authors.initials: B
authors.lastname: Moulard
authors.forename: F
authors.initials: F
authors.lastname: Salachas
authors.forename: B
authors.initials: B
authors.lastname: Chassande
authors.forename: V
authors.initials: V
authors.lastname: Briolotti
authors.forename: V
authors.initials: V
authors.lastname: Meininger
authors.forename: A
authors.initials: A
authors.lastname: Malafosse
authors.forename: W
authors.initials: W
authors.lastname: Camu
mesh_terms: D000328:Adult; D017668:Age of Onset; D002503:Centromere / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
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