Spinal muscular atrophy (SMA) is a common autosomal recessive genetic disorder characterized by degeneration of motor neurons and weakness and muscle atrophy. Approximately 95% of SMA patients are caused by homozygous deletions of the SMN1 gene, whereas the remaining 5% of patients harbor compound heterozygous mutations such as an SMN1 deletion allele and an intragenic mutation (insertions, deletions, or point mutations) in the other SMN1 allele. Although analysis for the SMN1/SMN2 copy number is relatively easy, molecular genetic testing for patients with subtle mutations is still compromised due to the presence of a highly homologous SMN2 gene. Herein, we analyzed the SMN1/SMN2 copy number by multiplex ligation-dependent probe amplification (MLPA) and subtle mutations by long-range PCR (LR-PCR) for two “nondeletion” SMA patients. We identified a missense mutation (c.280G > T, p. (Val94Phe)) and a splicing mutation c.*3+3A > T in SMN1 gene not previously described in the scientific literature. Giving the severe phenotype of the two patients, we speculated that these two point mutations could significantly affect the function of SMN proteins. Our results provide important information for genetic counseling and prenatal diagnosis in these families and enrich the SMN1 mutation database.

脊髓性肌萎缩症（SMA）是一种常见的常染色体隐性遗传疾病，其特征在于运动神经元变性，无力和肌肉萎缩。SMA患者的大约95％是由的纯合性缺失导致SMN1基因，而患者的其余5％怀有化合物杂合突变诸如SMN1缺失等位基因而在其他的基因内突变（插入，缺失，或点突变）的SMN1等位基因。尽管对SMN1 / SMN2拷贝数的分析相对容易，但是由于存在高度同源的SMN2基因，对具有细微突变的患者进行的分子遗传学测试仍然受到影响。在这里，我们分析了SMN1 / SMN2两名“非缺失” SMA患者通过多重连接依赖探针扩增（MLPA）获得的拷贝数和远程PCR（LR-PCR）产生的细微突变。我们在科学文献中未曾描述的SMN1基因中鉴定出一个错义突变（c.280G> T，p。（Val94Phe））和一个剪接突变c。* 3 + 3A>T 。考虑到两名患者的严重表型，我们推测这两个点突变可能会显着影响SMN蛋白的功能。我们的结果为这些家族的遗传咨询和产前诊断提供了重要信息，并丰富了SMN1突变数据库。