[PDF][PDF] Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number

PE McAndrew, DW Parsons, LR Simard… - The American Journal of …, 1997 - cell.com
PE McAndrew, DW Parsons, LR Simard, C Rochette, PN Ray, JR Mendell, TW Prior…
The American Journal of Human Genetics, 1997cell.com
The survival motor neuron (SMN) transcript is encoded by two genes, SMN T and SMN C.
The autosomal recessive proximal spinal muscular atrophy that maps to 5q12 is caused by
mutations in the SMN T gene. The SMN T gene can be distinguished from the SMN C gene
by base-pair changes in exons 7 and 8. SMN T exon 7 is not detected in∼ 95% of SMA
cases due to either deletion or sequence-conversion events. Small mutations in SMN T now
have been identified in some of the remaining nondeletion patients. However, there is no …
Summary
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 ∼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.
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