標題: Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening
作者: Chien, Yin-Hsiu
Chiang, Shu-Chuan
Weng, Wen-Chin
Lee, Ni-Chung
Lin, Ching-Jie
Hsieh, Wu-Shiun
Lee, Wang-Tso
Jong, Yuh-Jyh
Ko, Tsang-Ming
Hwu, Wuh-Liang
生醫工程研究所
Institute of Biomedical Engineering
公開日期: 1-Nov-2017
摘要: Objective To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS). Study design We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c. 888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c. 840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample. Results Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2. Conclusion Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives.
URI: http://dx.doi.org/10.1016/j.jpeds.2017.06.042
http://hdl.handle.net/11536/144186
ISSN: 0022-3476
DOI: 10.1016/j.jpeds.2017.06.042
期刊: JOURNAL OF PEDIATRICS
Volume: 190
起始頁: 124
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