Gene conversion at the SMN locus in autosomal recessive spinal muscular atrophy does not predict a mild phenotype.

Autosomal recessive proximal spinal muscular atrophy (SMA) is a disease of motor neuron death and a common cause of morbidity in childhood. It has been mapped to 5q13 and shown to be associated with deletions in a gene which has been called the survival motor neuron (SMN) gene. SMN exists in two copies in 5q13 and deletions in exon 7 and 8 of the telomeric copy (SMNtel) occur in over 90% of patients regardless of disease severity. In contrast, deletion of exon 7 and 8 of the centromeric copy of SMN is present in 3-5% of the normal population. In a minority of patients, exon 7 but not exon 8 of SMNtel appears deleted. The purpose of this study was to analyse this latter type of deletion in more detail. In all patients where there was absence of PCR amplification of exon 7 but not exon 8 of SMNtel this was found to be due to replacement with the homologous copy of SMNcen by a possible gene conversion event. This type of mutation occurred in all grades of severity of SMA.