Clinical and molecular genetic features of congenital spinal muscular atrophy

Abstract

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