Wijaya Yogik Onky Silvana, Purevsuren Jamiyan, Harahap Nur Imma Fatimah, Niba Emma Tabe Eko, Bouike Yoshihiro, Nurputra Dian Kesumapramudya, Rochmah Mawaddah Ar, Thursina Cempaka, Hapsara Sunartini, Yamaguchi Seiji, Nishio Hisahide, Shinohara Masakazu
Department of Community Medicine and Social Healthcare Science, Division of Epidemiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan;
Medical Genetics Laboratory, National Center for Maternal and Child Health, Khuvisgalchdyn Street, Bayangol District, Ulaanbaatar 16060, Mongolia;
Int J Neonatal Screen. 2020 May 29;6(2):43. doi: 10.3390/ijns6020043. eCollection 2020 Jun.
Spinal muscular atrophy (SMA) is a common neuromuscular disease with autosomal recessive inheritance. The disease gene, , is homozygously deleted in 95% of SMA patients. Although SMA has been an incurable disease, treatment in infancy with newly developed drugs has dramatically improved the disease severity. Thus, there is a strong rationale for newborn and carrier screening for SMA, although implementing SMA carrier screening in the general population is controversial. We previously developed a simple, accurate newborn SMA screening system to detect homozygous deletions using dried blood spots (DBS) on filter paper. Here, we modified our previous system to detect the heterozygous deletions of , which indicates SMA carrier status. The system involves a calibrator-normalized relative quantification method using quantitative nested PCR technology. Our system clearly separated the DBS samples with one copy (carrier status with a heterozygous deletion of ) from the DBS samples with two copies (non-carrier status with no deletion of ). We also analyzed DBS samples from SMA families, confirmed SMA in the affected children, and determined the carrier status of their parents based on the copy number. In conclusion, our system will provide essential information for risk assessment and genetic counseling, at least for SMA families.
脊髓性肌萎缩症（SMA）是一种常见的常染色体隐性遗传神经肌肉疾病。该疾病基因在95%的SMA患者中存在纯合缺失。尽管SMA曾是一种无法治愈的疾病，但使用新开发的药物在婴儿期进行治疗已显著改善了疾病严重程度。因此，对SMA进行新生儿和携带者筛查有充分的理由，尽管在普通人群中实施SMA携带者筛查存在争议。我们之前开发了一种简单、准确的新生儿SMA筛查系统，用于使用滤纸上的干血斑（DBS）检测纯合缺失。在此，我们对之前的系统进行了改进，以检测该基因的杂合缺失，这表明SMA携带者状态。该系统涉及一种使用定量巢式PCR技术的校准物标准化相对定量方法。我们的系统能够清晰地将含有一个该基因拷贝的DBS样本（杂合缺失的携带者状态）与含有两个该基因拷贝的DBS样本（无缺失的非携带者状态）区分开来。我们还分析了来自SMA家庭的DBS样本，确认了患病儿童的SMA，并根据该基因拷贝数确定了其父母的携带者状态。总之，我们的系统将为风险评估和遗传咨询提供重要信息，至少对于SMA家庭是如此。
