2016 Volume 48 Issue 5 Pages 343-346
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration or loss of anterior horn cells in the spinal cord. The SMN1 gene is considered to be responsible for SMA, because 95% of SMA patients show homozygous deletion of SMN1. In this study, we examined the clinical course of an SMA type 1 patient who retains one allele of SMN1, identifying an intragenic mutation in the retained allele.
The patient was a Japanese boy with no family history of neuromuscular disorders. He showed generalized muscle weakness and respiratory failure from the neonatal period. He underwent non-invasive positive pressure ventilation at 20 days old. His respiratory failure rapidly deteriorated, and endotracheal intubation-positive pressure ventilation was needed at 3 months old, followed by tracheostomy-positive pressure ventilation at 6 months old. For diagnosis, the SMN1 deletion screening test was performed, but the result was negative. Further analysis showed absence of one SMN1 allele, and presence of an intragenic mutation (c.819_820insT) in the retained SMN1 allele that disrupts the C-terminal domain of the SMN protein. He was subsequently diagnosed as having SMA type 1 with a compound heterozygous genotype. We conclude that an intragenic mutation in the retained SMN1 allele caused SMA in the index patient, and suggest that this mutation is a critical factor in determining disease severity.
