A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Objectives and Ethics
2.2. SMA Patients and Non-SMA Controls
2.3. Newborn Infants
2.4. SMN1-Deletion Detection System
2.4.1. Targeted Pre-Amplification of the SMN Genes
2.4.2. Gene-Specific Amplification of SMN1 Exon 7
2.5. Newborn Screening Study Design
2.6. Follow-Up Study of the Infants Screened for SMA
2.7. Statistical Analysis
3. Results
3.1. Validation Study
3.2. Newborn Screening for SMA
3.3. Follow-Up Study of the Infants Screened for SMA
4. Discussion
4.1. Targeted Pre-Amplification of SMN1/SMN2 Sequence
4.2. Modified Competitive Oligonucleotide Priming-PCR (mCOP-PCR)
4.3. Accurate Detection System for SMN1 Deletion
4.4. Robust System for SMA Newborn Screening Using DBS
4.5. Limitations of SMN1-Deletion Detection as an SMA Screening Strategy
5. Conclusions
6. Patents
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
- Japanese Red Cross Katsushika Maternity Hospital: Sakae Kumasaka, Chisako Mitsuishi;
- Matsuyama Red Cross Hospital: Yoichi Kondo;
- Chibune General Hospital: Akihiro Takatera;
- St. Marianna University School of Medicine: Isamu Hokuto;
- Kurashiki Medical Center: Tetsuro Fujino, Nobuyoshi Mimaki, Noriko Yanazaki;
- National Hospital Organization Okayama Medical Center: Makoto Nakamura, Akihito Takeuchi;
- Shimane Prefectural Central Hospital: Fumihide Kato;
- Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine: Emma Tabe Eko Niba, Hisahide Nishio, Masakazu Shinohara, Izumi Takayama, Yogik Onky Silvana Wijaya;
- Department of Pediatrics, Kobe University Graduate School of Medicine: Kazumichi Fujioka, Kazumoto Iijima;
- Kurashiki Central Hospital: Akihito Takahashi;
- Okayama University Hospital: Daisaku Morimoto, Yosuke Washio;
- Japan Community Health Care Organization Kyushu Hospital: Yasuhiko Takahashi, Junko Yamamoto;
- Fukuoka Children’s Hospital: Yasushi Takahata;
- Nihon University School of Medicine: Ichiro Morioka, Nobuhiko Nagano;
- Hyogo Prefectural Kobe Children’s Hospital Perinatal Center: Hideto Nakao, Tomoyuki Yokota, Seiji Yoshimoto;
- Tosei General Hospital: Kuniko Ieda;
- Hiroshima University Graduate School of Biomedical and Health Sciences: Norioki Ohno;
- Hokkaido University Hospital: Kazutoshi Cho, Hideaki Shiraishi;
- Toyohashi municipal hospital: Norihisa Koyama, Mari Sugimoto;
- Saga University: Manabu Iwanaga, Muneaki Matsuo;
- Jichi Medical School: Hitoshi Osaka, Hironori Shimozawa, Takanori Yamagata;
- Almeida Memorial Hospital: Naoki Fukushima;
- Toyooka Hospital: Masaaki Ueda;
- Omihachiman Community Medical Center: Shinobu Yoshida;
- Hyogo College of Medicine: Hideki Shimomura, Yasuhiro Takeshima;
- Nagasaki University Hospital: Fumiko Kinoshita, Tatsuharu Sato;
- Juntendo University Nerima Hospital: Shinichi Niijima, Noboru Yoshida;
- Tokyo Metropolitan Ohtsuka Hospital: Ken Masunaga;
- National Hospital Organization Nagasaki Medical Center: Mikihiro Aoki;
- Kakogawa Central City Hospital: Takeshi Morisawa;
- Niigata City General Hospital: Yoshihisa Nagayama;
- Chiba Children’s Hospital: Kei Murayama, Tomoko Tsuruoka;
- Yokosuka General Hospital Uwamachi: Tomoyuki Miyamoto;
- Kouseiren Takaoka Hospital: Hiroaki Imamura, Jiro Ogawa;
- Hokkaido Medical Center for Child Health and Rehabilitation: Hideomi Asanuma, Shuku Ishikawa;
- Sapporo Medical University Hospital: Masaki Kobayashi;
- Japanese Red Cross Nagoya Daini Hospital: Taihei Tanaka, Takaharu Yamada;
- Akita University Graduate School of Medicine: Hiroyuki Adachi, Atsuko Noguchi, Tsutomu Takahashi;
- Japanese Red Cross Saitama Hospital: Yuko Sato;
- Graduate School of Medicine, University of the Ryukyus: Koichi Nakanishi, Tomohide Yoshida;
- Numazu City Hospital: Masao Murabayashi;
- Sapporo City General Hospital: Masato Mizushima, Tatsuo Satomi;
- Maternal & Child Health Center Aiiku Hospital: Shinya Hayashida;
- Hiroshima City Hiroshima Citizens Hospital: Yutaka Nishimura;
- Juntendo University Shizuoka Hospital: Masato Kantake;
- Yamaguchi University Hospital: Sasagu Kimura, Kazumasa Takahashi;
- National Center for Child Health and Development: Go Tajima;
- Kobe Pharmaceutical University: Atsuko Takeuchi
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PCR–RFLP (Fresh Blood) | Total | ||
---|---|---|---|
SMN1(–) | SMN1(+) | ||
Real-time mCOP-PCR (DBS) | |||
SMN1(–) | 50 | 0 | 50 |
SMN1(+) | 0 | 50 | 50 |
Total | 50 | 50 | 100 |
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Shinohara, M.; Niba, E.T.E.; Wijaya, Y.O.S.; Takayama, I.; Mitsuishi, C.; Kumasaka, S.; Kondo, Y.; Takatera, A.; Hokuto, I.; Morioka, I.; et al. A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study. Int. J. Neonatal Screen. 2019, 5, 41. https://doi.org/10.3390/ijns5040041
Shinohara M, Niba ETE, Wijaya YOS, Takayama I, Mitsuishi C, Kumasaka S, Kondo Y, Takatera A, Hokuto I, Morioka I, et al. A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study. International Journal of Neonatal Screening. 2019; 5(4):41. https://doi.org/10.3390/ijns5040041
Chicago/Turabian StyleShinohara, Masakazu, Emma Tabe Eko Niba, Yogik Onky Silvana Wijaya, Izumi Takayama, Chisako Mitsuishi, Sakae Kumasaka, Yoichi Kondo, Akihiro Takatera, Isamu Hokuto, Ichiro Morioka, and et al. 2019. "A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study" International Journal of Neonatal Screening 5, no. 4: 41. https://doi.org/10.3390/ijns5040041
APA StyleShinohara, M., Niba, E. T. E., Wijaya, Y. O. S., Takayama, I., Mitsuishi, C., Kumasaka, S., Kondo, Y., Takatera, A., Hokuto, I., Morioka, I., Ogiwara, K., Tobita, K., Takeuchi, A., Nishio, H., & for the SMA-NBS PILOT STUDY GROUP. (2019). A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study. International Journal of Neonatal Screening, 5(4), 41. https://doi.org/10.3390/ijns5040041