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A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study
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, part...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510215/ https://www.ncbi.nlm.nih.gov/pubmed/33072999 http://dx.doi.org/10.3390/ijns5040041 |
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author | Shinohara, Masakazu Niba, Emma Tabe Eko Wijaya, Yogik Onky Silvana Takayama, Izumi Mitsuishi, Chisako Kumasaka, Sakae Kondo, Yoichi Takatera, Akihiro Hokuto, Isamu Morioka, Ichiro Ogiwara, Kazutaka Tobita, Kimimasa Takeuchi, Atsuko Nishio, Hisahide |
author_facet | Shinohara, Masakazu Niba, Emma Tabe Eko Wijaya, Yogik Onky Silvana Takayama, Izumi Mitsuishi, Chisako Kumasaka, Sakae Kondo, Yoichi Takatera, Akihiro Hokuto, Isamu Morioka, Ichiro Ogiwara, Kazutaka Tobita, Kimimasa Takeuchi, Atsuko Nishio, Hisahide |
author_sort | Shinohara, Masakazu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7510215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75102152020-10-15 A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study Shinohara, Masakazu Niba, Emma Tabe Eko Wijaya, Yogik Onky Silvana Takayama, Izumi Mitsuishi, Chisako Kumasaka, Sakae Kondo, Yoichi Takatera, Akihiro Hokuto, Isamu Morioka, Ichiro Ogiwara, Kazutaka Tobita, Kimimasa Takeuchi, Atsuko Nishio, Hisahide Int J Neonatal Screen Article 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. MDPI 2019-11-12 /pmc/articles/PMC7510215/ /pubmed/33072999 http://dx.doi.org/10.3390/ijns5040041 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shinohara, Masakazu Niba, Emma Tabe Eko Wijaya, Yogik Onky Silvana Takayama, Izumi Mitsuishi, Chisako Kumasaka, Sakae Kondo, Yoichi Takatera, Akihiro Hokuto, Isamu Morioka, Ichiro Ogiwara, Kazutaka Tobita, Kimimasa Takeuchi, Atsuko Nishio, Hisahide A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study |
title | A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study |
title_full | A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study |
title_fullStr | A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study |
title_full_unstemmed | A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study |
title_short | A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study |
title_sort | novel system for spinal muscular atrophy screening in newborns: japanese pilot study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510215/ https://www.ncbi.nlm.nih.gov/pubmed/33072999 http://dx.doi.org/10.3390/ijns5040041 |
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