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. (C) 2007 Elsevier B.V. All rights reserved.