title: Technical standards and guidelines for spinal muscular atrophy testing.
abstract: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. The disease is characterized by progressive symmetrical muscle weakness resulting from the degeneration and loss of anterior horn cells in the spinal cord and brainstem nuclei. The disease is classified on the basis of age of onset and clinical course. Two almost identical SMN genes are present on 5q13: the SMN1 gene, which is the spinal muscular atrophy-determining gene, and the SMN2 gene. The homozygous absence of the SMN1 exon 7 has been observed in the majority of patients and is being used as a reliable and sensitive spinal muscular atrophy diagnostic test. Although SMN2 produces less full-length transcript than SMN1, the number of SMN2 copies has been shown to modulate the clinical phenotype. Carrier detection relies on the accurate determination of the SMN1 gene copies. This document follows the outline format of the general Standards and Guidelines for Clinical Laboratories. It is designed to be a checklist for genetic testing professionals who are already familiar with the disease and methods of analysis.
authors.affiliation: Department of Pathology, Ohio State University, 1645 Neil Ave, Columbus, OH 43210, USA. Thomas.prior@osumc.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Prior
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Nagan
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Sugarman
authors.forename: Sat Dev
authors.initials: SD
authors.lastname: Batish
authors.forename: Corey
authors.initials: C
authors.lastname: Braastad
mesh_terms: D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards; D004252:DNA Mutational Analysis; D018628:Gene Dosage; D005820:Genetic Testing / Q000379:methods* / Q000592:standards*; D017408:Guidelines as Topic; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein