title: Spinal muscular atrophy diagnostics.
abstract: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN), which exists in 2 nearly identical copies (SMN1 and SMN2). Exon 7 of SMN1 is homozygously absent in about 95% of spinal muscular atrophy patients, whereas the loss of SMN2 does not cause spinal muscular atrophy. Small mutations are found in the other 5% of affected patients, and these mutations cluster in the 3' end of SMN1, a region important for protein oligomerization. SMN1 dosage testing can be used to determine the SMN1 copy number and to detect spinal muscular atrophy carriers and affected compound heterozygotes. Dosage testing is compromised by the presence of 2 SMN1 copies per chromosome, which occurs in about 2% of carriers. Finally, although SMN2 produces less full-length transcript than SMN1, the number of SMN2 copies modulates the phenotype.
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio 43210, USA. thomas.prior@osumc.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Prior
mesh_terms: D002648:Child; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000592:standards; D042241:Early Diagnosis; D018628:Gene Dosage / Q000235:genetics; D006580:Genetic Carrier Screening / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000592:standards; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; 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