APPARENT GENE CONVERSIONS INVOLVING THE SMN GENE IN THE REGION OF THESPINAL MUSCULAR-ATROPHY LOCUS ON CHROMOSOME-5

The survival motor neuron (SMN) gene has been described as a determini ng gene for spinal muscular atrophy (SMA). SMN has a closely flanking, nearly identical copy ((C)BCD541). Gene and copy gene can be discrimi nated by sequence differences in exons 7 and 8. The large majority of SMA patients show homozygous deletions of at least exons 7 and 8 of th e SMN gene. A minority of patients show absence of SMN exon 7 but rete ntion of exon 8. This is explained by results of our present analysis of 13 such patients providing evidence for apparent gene-conversion ev ents between SMN and the centromeric copy gene. Instead of applying a separate analysis for absence or presence of SMN exons 7 and 8, we use d a contiguous PCR from intron 6 to exon 8. In every case we found a c himeric gene with a fusion of exon 7 of the copy gene and exon 8 of SM N and absence of a normal SMN gene. Similar events, including the fusi on counterpart, were observed in a group of controls, although in the presence of a normal SMN gene. Chimeric genes as the result of fusions of parts of SMN and (C)BCD541 apparently are far from rare and may pa rtly explain the frequently observed SMN deletions in SMA patients.