Gambardella A, Mazzei R, Toscano A, Annesi G, Pasqua A, Annesi F, Quattrone F, Oliveri R L, Valentino P, Bono F, Aguglia U, Zappia M, Vita G, Quattrone A
Institute of Neurology, School of Medicine, Catanzaro, Italy.
Ann Neurol. 1998 Nov;44(5):836-9. doi: 10.1002/ana.410440522.
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 features of SMA types II and III, who carried a homozygous deletion of SMN(T) exon 8 but retained SMN(T) exon 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) of exon 7. The subsequent restriction analysis failed to show any products of telomeric exon 7, as the site for primer 541C1120 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 more severely affected child also showed a deletion of the neuronal apoptosis inhibitory protein (NAIP) gene. 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.
常染色体隐性遗传性脊髓性肌萎缩症（SMA）患者通常携带端粒生存运动神经元（SMN(T)）基因第7和第8外显子的纯合缺失，尽管从未发现过单独的SMN(T)第8外显子缺失。我们现在报告2例具有II型和III型SMA典型特征的患者，他们携带SMN(T)第8外显子的纯合缺失，但保留了SMN(T)第7外显子。重要的是，为了排除端粒第8外显子的序列转换事件，我们扩增了一个跨越SMN基因第7和第8外显子的片段。将得到的1010碱基对（bp）片段进行第7外显子的巢式聚合酶链反应（PCR）。随后的限制性分析未能显示端粒第7外显子的任何产物，因为引物541C1120的位点在两个等位基因中均缺失。这些发现表明SMN(T)第8外显子存在纯合缺失。对克隆的1010-bp片段进行直接测序进一步证实这2例SMA患者不具有端粒第8外显子。病情较重的患儿还显示出神经元凋亡抑制蛋白（NAIP）基因的缺失。目前的发现提供了证据，表明单独的SMN(T)第8外显子缺失与较轻亚型的SMA相关。我们的数据还表明，NAIP基因的额外缺失会加重疾病的严重程度。
