title: Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number.
abstract: The survival motor neuron (SMN) transcript is encoded by two genes, SMNT and SMNC. The autosomal recessive proximal spinal muscular atrophy that maps to 5q12 is caused by mutations in the SMNT gene. The SMNT gene can be distinguished from the SMNC gene by base-pair changes in exons 7 and 8. SMNT exon 7 is not detected in approximately 95% of SMA cases due to either deletion or sequence-conversion events. Small mutations in SMNT now have been identified in some of the remaining nondeletion patients. However, there is no reliable quantitative assay for SMNT, to distinguish SMA compound heterozygotes from non-5q SMA-like cases (phenocopies) and to accurately determine carrier status. We have developed a quantitative PCR assay for the determination of SMNT and SMNC gene-copy number. This report demonstrates how risk estimates for the diagnosis and detection of SMA carriers can be modified by the accurate determination of SMNT copy number.
authors.affiliation: Department of Pathology, Ohio State University, Columbus 43210, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: McAndrew
authors.forename: D W
authors.initials: DW
authors.lastname: Parsons
authors.forename: L R
authors.initials: LR
authors.lastname: Simard
authors.forename: C
authors.initials: C
authors.lastname: Rochette
authors.forename: P N
authors.initials: PN
authors.lastname: Ray
authors.forename: J R
authors.initials: JR
authors.lastname: Mendell
authors.forename: T W
authors.initials: TW
authors.lastname: Prior
authors.forename: A H
authors.initials: AH
authors.lastname: Burghes
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005091:Exons; D005260:Female; D018628:Gene Dosage; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D018570:Risk Assessment; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D014158:Transcription, Genetic
chemical_list: C505032:CFTR protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D009692:Nucleic Acid Heteroduplexes; 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; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA