A feasibility study for the newborn screening of spinal muscular atrophy.
OBJECTIVE
The natural history of spinal muscular atrophy suggests that for maximum effect, therapeutics will need to be administered in the earliest phases of the disease. This will require the adoption of techniques for the genetic analysis of affected individuals at the newborn stage. Our objective was to examine the feasibility surrounding the newborn screening for spinal muscular atrophy.


METHODS
We investigated the application of real-time polymerase chain reaction technology for newborn screening. A multiplex assay was designed to identify homozygous deletions in SMN1 exon 7 and validated using 266 samples with defined SMN1 and SMN2 copy numbers. Sensitivity and specificity were then evaluated as part of a newborn screening strategy using DNA from 153 blood spots.


RESULTS
Real-time technology validation demonstrated correct exclusion of all normal and carrier samples, and identified the homozygous SMN1 exon 7 deletions in all 32 affected samples. In the series of blood spots, all 59 affected samples were correctly identified yielding an analytic sensitivity of 100%; 56 normal and 39 carrier samples were correctly excluded yielding an analytic specificity of 100% for this blood spot series.


CONCLUSIONS
We demonstrate that effective molecular technology exists and that ethics may soon warrant the newborn screening of spinal muscular atrophy.
Pyatt
Robert E
RE
Department of Pathology, Ohio State University, Columbus, Ohio 43210, USA.
Prior
Thomas W
TW
D003199:Computer Systems; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D005240:Feasibility Studies; D017353:Gene Deletion; D018628:Gene Dosage; D005820:Genetic Testing / Q000191:economics / Q000941:ethics; D006801:Humans; D007231:Infant, Newborn; D009419:Nerve Tissue Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000235:genetics; D043262:Ribonuclease P / Q000235:genetics; D055532:SMN Complex Proteins; D012680:Sensitivity and Specificity; D014897:Spinal Muscular Atrophies of Childhood / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
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; D043262:Ribonuclease P