Association between centromeric deletions of theSMN gene and sporadic adult-onset lower motor neuron disease
| Autor: | Bénédicte Chassande, William Camu, Valerie Briolotti, Vincent Meininger, François Salachas, Bruno Moulard, Alain Malafosse |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Centromere Population Nerve Tissue Proteins Biology Central nervous system disease Degenerative disease medicine Humans Age of Onset Motor Neuron Disease Amyotrophic lateral sclerosis Cyclic AMP Response Element-Binding Protein education Family Health Genetics education.field_of_study Polymorphism Genetic Genetic heterogeneity Homozygote RNA-Binding Proteins SMN Complex Proteins Spinal muscular atrophy Middle Aged Motor neuron medicine.disease Survival of Motor Neuron 1 Protein Survival of Motor Neuron 2 Protein medicine.anatomical_structure Neurology Female Neurology (clinical) Age of onset Gene Deletion |
| Zdroj: | Annals of Neurology. 43:640-644 |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.410430513 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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