Significant increase in the number of the SMN2 gene copies in an adult-onset Type III spinal muscular atrophy patient with homozygous deletion of the NAIP gene

Abstract

The patient was a 57-year-old Japanese man who gradually developed muscle atrophy and weakness in the trunk and limbs since the age of 20 years and was wheelchair bound at the age of 56 years. The gene copy number assay confirmed the combined homozygous deletion of the survival motor neuron (SMN) 1 and neuronal apoptosis inhibitory protein (NAIP) genes and showed the presence of 4 copies of the SMN2 gene. In this patient, the significant increase in the number of the SMN2 gene copies should compensate for the homozygous deletion of the SMN1 gene and make his disease milder despite the absence of the NAIP gene. Taken together with our previous data, we may reasonably hypothesize that the SMN2 gene copy number is more critical in determining the severity of the disease compared to the NAIP genotype.