title: Implementation of SMA carrier testing in genetic laboratories: comparison of two methods for quantifying the SMN1 gene.
abstract: The degeneration and loss of motor neurons of the anterior horn characterize children affected with spinal muscular atrophy (SMA). Mutations in the survival motor neuron gene (SMN1) are determinant for the development of the disease whereas the number of copies of SMN2, the highly homologous copy of SMN1, plays a role as a phenotypic modifier factor. The detection of SMN1 homozygous deletions is the typical test for SMA diagnosis. Owing to the limitation of this test for carrier and heterozygous deletion analysis, the demand of SMN1 quantitative tests is permanently growing. The high incidence of SMA, the notable carrier frequency, the severity of the disease, and the lack of effective treatment may justify the implementation of such an analysis in DNA diagnostic labs. The advantages and disadvantages of two reliable quantitative methods were evaluated. One of these is a competitive PCR protocol using internal standards and a genomic sequence as a reference. The other method is a real-time PCR employing an external standard as a reference. Both methods present sufficient advantages for incorporation into molecular genetic diagnostic labs. The possibility of studying samples from different labs, the versatility and reproducibility of the analysis, and cost-benefit calculations must be considered in the final choice.
authors.affiliation: Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Ivon
authors.initials: I
authors.lastname: Cuscó
authors.forename: María J
authors.initials: MJ
authors.lastname: Barceló
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000235:genetics; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing / Q000191:economics; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D016601:RNA-Binding Proteins; D015203:Reproducibility of Results; 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; D004247:DNA