Detection of intragenic SMN1 mutations in spinal muscular atrophy patients with a single copy of SMN1.

Proximal spinal muscular atrophy is an autosomal recessive disorder characterized by symmetrical muscle weakness due to degeneration of alpha motor neurons in the spinal cord. Homozygous deletions in the SMN1 have been reported in more than 90% of spinal muscular atrophy cases. Compound heterozygous patients account for approximately 4% of spinal muscular atrophy cases. In this study, we performed a quantitative test in 20 of 87 spinal muscular atrophy patients who did not have homozygous deletion of SMN1. Mutation screening of SMN1 gene was performed in 4 patients who have only 1 copy of SMN1 to identify intragenic mutations. In addition to a previously described missense mutation in exon 4 (p.A188S/ c.562G>T), we identified 2 novel mutations including a single nucleotide insertion in exon 7 (c.861_862insT/p.R288X) and a deletion of nucleotide G in exon 3 (c.286delG/p.D96Tfs*53). Our results suggested that about 4% of spinal muscular atrophy patients have subtle mutations and might be considered in laboratory examination.