A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study

Abstract

by Masakazu Shinohara,Emma Tabe Eko Niba,Yogik Onky Silvana Wijaya,Izumi Takayama,Chisako Mitsuishi,Sakae Kumasaka,Yoichi Kondo,Akihiro Takatera,Isamu Hokuto,Ichiro Morioka,Kazutaka Ogiwara,Kimimasa Tobita,Atsuko Takeuchi,Hisahide Nishio andfor the SMA-NBS PILOT STUDY GROUP
Int. J. Neonatal Screen. 2019, 5(4), 41; https://doi.org/10.3390/ijns5040041 - 13 May 2023
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Abstract
Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by SMN1 gene deletion/mutation. The drug nusinersen modifies SMN2 mRNA splicing, increasing the production of the full-length SMN protein. Recent studies have demonstrated the beneficial effects of nusinersen in patients with SMA, particularly when treated in early infancy. Because nusinersen treatment can alter disease trajectory, there is a strong rationale for newborn screening. In the current study, we validated the accuracy of a new system for detecting SMN1 deletion (Japanese patent application No. 2017-196967, PCT/JP2018/37732) using dried blood spots (DBS) from 50 patients with genetically confirmed SMA and 50 controls. Our system consists of two steps: (1) targeted pre-amplification of SMN genes by direct polymerase chain reaction (PCR) and (2) detection of SMN1 deletion by real-time modified competitive oligonucleotide priming-PCR (mCOP-PCR) using the pre-amplified products. Compared with PCR analysis results of freshly collected blood samples, our system exhibited a sensitivity of 1.00 (95% confidence interval [CI] 0.96–1.00) and a specificity of 1.00 (95% CI 0.96–1.00). We also conducted a prospective SMA screening study using DBS from 4157 Japanese newborns. All DBS tested negative, and there were no screening failures. Our results indicate that the new system can be reliably used in SMA newborn screening. Full article
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15 pages, 1543 KiB
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