EVIDENCE FOR COMPOUND HETEROZYGOSITY CAUSING MILD AND SEVERE FORMS OFAUTOSOMAL RECESSIVE SPINAL MUSCULAR-ATROPHY

Spinal muscular atrophy is an autosomal recessive disease of motor neu rone degeneration which shows a variable phenotype. Two candidate gene s show deletions in affected subjects but with no distinction between different forms of the disease. We report an unusual family in which m ild and severe SMA coexists and patients are deleted for the SMN gene. The father is affected with late onset SMA; therefore this family sho ws pseudodominant inheritance, When typed using closely linked flankin g markers the severely affected son does not share the same haplotype as his sib, who is deleted for SMN but shows no signs yet of SMA. This supports the hypothesis that differences in SMA phenotype can be expl ained by a multiple allele model.