Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene

Abstract Patients with autosomal recessive spinal muscular atrophy (SMA) usually carry a homozygous deletion of exons 7 and 8 of the telomeric survival motor neuron (SMN T ) gene, although an isolated deletion of SMN T exon 8 has never been found. We now report on 2 patients with the typical fetures of SMA types II and III, who carried a homozygous deletion of SMN T exon 8 but retained SMN T 7. Importantly, to exclude a sequence conversion event of telomeric exon 8, we amplified a fragment that spanned exons 7 and 8 of the SMN gene. The resulting 1,010‐base pair (bp) fragments were subjected to nested polymerase chain reaction (PCR) on exon 7. The subsequent restriction analysis failed to show any products of telomeric exon 7, as the site for primer 541 C1120 was lost in both alleles. These findings indicate a homozygous deletion of SMN T exon 8. Direct sequencing of the cloned 1,010‐bp fragment further confirmed that these 2 SMA patients did not possess telomeric exon 8. The present findings provide evidence that an isolated deletion of SMN T exon 8 is associated with the milder subtypes of SMA. Our data also demonstrate that the additional deletion of the NAIP gene exacerbates the severity of the disease.