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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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