A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study
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
Japanese Red Cross Katsushika Maternity Hospital, 5-11-12 Tateishi, Katsushika-ku, Tokyo 124-0012, Japan
Matsuyama Red Cross Hospital, 1 Bunkyo-cho, Matsuyama 790-8524, Japan
Chibune General Hospital, 3-2-39 Fukumachi, Nishiyodogawa-ku, Osaka 555-0034, Japan
Department of Pediatrics, St. Marianna University School of Medicine, 2-16-1 Sugao, Kawasaki 216-8511, Japan
Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1 Oyaguchi kamicho, Itabashi-ku, Tokyo 173-8610, Japan
Biogen Japan Ltd., 1-4-1 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan
Kobe Pharmaceutical University, 4-19-1, Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan
Department of Occupational Therapy, Faculty of Rehabilitation, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan
Author to whom correspondence should be addressed.
A complete list of the centres and investigators in the SMA-NBS PILOT STUDY GROUP is provided in Appendix A.
Int. J. Neonatal Screen. 2019, 5(4), 41; https://doi.org/10.3390/ijns5040041
Received: 17 October 2019 / Accepted: 6 November 2019 / Published: 12 November 2019
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.