GENE DELETIONS IN SPINAL MUSCULAR-ATROPHY

Two candidate genes (NAIP and SMN) have recently been reported for chi ldhood onset spinal muscular atrophy (SMA). Although affected subjects show deletions of these genes, these deletions can lead to either a v ery mild or a severe phenotype. We have analysed a large number of cli nically well defined patients, carriers, and normal controls to assess the frequency and extent of deletions encompassing both of these gene s. A genotype analysis indicates that more extensive deletions are see n in the severe form of SMA than in the milder forms. In addition, 1.9 % of phenotypically normal carriers are deleted for the NAIP gene; no carriers were deleted for the SMN gene. Our data suggest that deletion s in both of these genes, using the currently available assays, are as sociated with both a severe and very mild phenotype.