CLINICAL AND MOLECULAR-GENETIC FEATURES OF CONGENITAL SPINAL MUSCULAR-ATROPHY

A neonate presented with the fetal hypokinesia sequence and signs of s pinal muscular atrophy (SMA). Severe pathological changes including ba llooned neurons and neuronophagia were found not only in the motor ner ve nuclei but also in the thalamic, cerebellar, and brainstem nuclei a s well as in the dorsal root ganglia Direct DNA analysis showed the pr esence of a chimeric SMN gene, with a rearrangement occurring between exon 7 of the centromeric SMN gene and exon 8 of the telomeric SMN gen e. Circumstantial evidence suggests that only a single copy of this ge ne is present, with transcriptional characteristics of a centromeric S MN gene. In addition, a homozygous deletion in the NAIP genes was demo nstrated. This observation demonstrates that at least some cases with fetal hypokinesia and SMA may represent the severe end of a spectrum o f disorders caused by deletions in the SMA locus on chromosome 5q13. I n addition, these findings are compatible with a modifying role for th e centromeric SMN genes and the NAIP genes in the severity of the SMA phenotype.