A new splice site mutation in the SMN1 gene causes discrepant results in SMN1 deletion screening approaches.
In most patients with infantile spinal muscular atrophy (SMA) both exons 7 and 8 of the SMN1 gene are deleted, but the deletion may also be restricted to exon 7. We report on an SMA type I patient who was initially diagnosed to be homozygous for an exon 7 deletion only. However, multiplex ligation-dependent probe amplification (MLPA) analyses revealed a heterozygous deletion of exons 7 and 8 of the SMN1 gene. By sequencing a new subtle splice site mutation (IVS6-2A>G) was identified. This variant affects the target sequence of oligonucleotides of all applied tests in a way that it has contrary effects on the efficiencies of the different assays. The results have major impacts on genetic counselling and carrier detection of the patient's paternal relatives.
D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D017809:Fatal Outcome; D005820:Genetic Testing / Q000379:methods / Q000592:standards*; D006801:Humans; D007223:Infant; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation; D012326:RNA Splicing / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000592:standards; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein