Lin Yiming, Lin Chien-Hsing, Yin Xiaoshan, Zhu Lin, Yang Jianbin, Shen Yuyan, Yang Chiju, Chen Xigui, Hu Haili, Ma Qingqing, Shi Xueqin, Shen Yaping, Hu Zhenzhen, Huang Chenggang, Huang Xinwen
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Neonatal Disease Screening Center, Quanzhou Maternity and Children's Hospital, Quanzhou, China.
Front Genet. 2019 Dec 17;10:1255. doi: 10.3389/fgene.2019.01255. eCollection 2019.
Spinal muscular atrophy (SMA) is the most common neurodegenerative disorder and the leading genetic cause of infant mortality. Early detection of SMA through newborn screening (NBS) is essential to selecting pre-symptomatic treatment and ensuring optimal outcome, as well as, prompting the urgent need for effective screening methods. This study aimed to determine the feasibility of applying an Agena iPLEX SMA assay in NBS for SMA in China. We developed an Agena iPLEX SMA assay based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and evaluated the performance of this assay through assessment of 167 previously-genotyped samples. Then we conducted a pilot study to apply this assay for SMA NBS. The and copy number of screen-positive patients were determined by multiplex ligation-dependent probe amplification analysis. The sensitivity and specificity of the Agena iPLEX SMA assay were both 100%. Three patients with homozygous deletion were successfully identified and conformed by multiplex ligation-dependent probe amplification analysis. Two patients had two copies, which was correlated with severe SMA type I phenotype; both of them exhibited neurogenic lesion and with decreased muscle power. Another patient with four copies, whose genotype correlated with milder SMA type III or IV phenotype, had normal growth and development without clinical symptoms. The Agena iPLEX SMA assay is an effective and reliable approach for population-based SMA NBS. The first large-scale pilot study using this assay in the Mainland of China showed that large-scale implementation of population-based NBS for SMA is feasible.
脊髓性肌萎缩症（SMA）是最常见的神经退行性疾病，也是婴儿死亡的主要遗传原因。通过新生儿筛查（NBS）早期发现SMA对于选择症状前治疗和确保最佳治疗效果至关重要，同时也迫切需要有效的筛查方法。本研究旨在确定在中国将Agena iPLEX SMA检测应用于SMA的新生儿筛查的可行性。我们基于基质辅助激光解吸/电离飞行时间质谱开发了一种Agena iPLEX SMA检测方法，并通过对167个先前已进行基因分型的样本进行评估来评价该检测方法的性能。然后我们进行了一项试点研究，将该检测方法应用于SMA的新生儿筛查。通过多重连接依赖探针扩增分析确定筛查阳性患者的 和 拷贝数。Agena iPLEX SMA检测的灵敏度和特异性均为100%。成功鉴定出3例纯合 缺失患者，并通过多重连接依赖探针扩增分析得以证实。2例患者有两个 拷贝，这与严重的I型SMA表型相关；他们均表现出神经源性病变且肌力下降。另1例有四个 拷贝的患者，其基因型与较轻的III型或IV型SMA表型相关，生长发育正常且无临床症状。Agena iPLEX SMA检测是一种用于基于人群的SMA新生儿筛查的有效且可靠的方法。在中国内地首次使用该检测方法进行的大规模试点研究表明，基于人群的SMA新生儿筛查大规模实施是可行的。
