A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study
| Autor: | Yogik Onky Silvana Wijaya, Kimimasa Tobita, Sakae Kumasaka, Ichiro Morioka, Akihiro Takatera, Emma Tabe Eko Niba, Atsuko Takeuchi, Yoichi Kondo, Chisako Mitsuishi, Hisahide Nishio, Isamu Hokuto, Izumi Takayama, Kazutaka Ogiwara, Masakazu Shinohara |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty SMN1 030105 genetics & heredity mCOP-PCR medicine.disease_cause Gastroenterology Article law.invention 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) law Internal medicine Medicine Polymerase chain reaction spinal muscular atrophy Newborn screening Mutation business.industry Obstetrics and Gynecology Spinal muscular atrophy medicine.disease SMA Confidence interval nervous system diseases Pediatrics Perinatology and Child Health Nusinersen business 030217 neurology & neurosurgery SMN2 |
| Zdroj: | International Journal of Neonatal Screening Volume 5 Issue 4 |
| ISSN: | 2409-515X |
| DOI: | 10.3390/ijns5040041 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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