Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome

We have analyzed the survival motor neuron gene (SMN1) dosage in 100 parent s of children with homozygous SMN1 deletions. Of these parents, 96 (96%) de monstrated the expected one-copy SMN1 carrier genotype. However, four paren ts (4%) were observed to have a normal two-copy SMN1 dosage. The presence o f two intact SMN1 genes in the parent of an affected child indicates either the occurrence of a de novo mutation event or a situation in which one chr omosome has two copies of SMN1, whereas the other is null. We have separate d individual chromosomes from two of these parents with two-copy SMN1 dosag e by somatic cell hybridization and have employed a modified quantitative d osage assay to provide direct evidence that one parent is a two-copy/zero-c opy SMN1 carrier, whereas the other parent had an affected child as the res ult of a de novo mutation. These findings are important for assessing the r ecurrence risk of parents of children with spinal muscular atrophy and for providing accurate family counseling.