A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study

被引：26

作者：

Shinohara, Masakazu ^{[1
]}

Niba, Emma Tabe Eko ^{[1
]}

Wijaya, Yogik Onky Silvana ^{[1
]}

Takayama, Izumi ^{[1
]}

Mitsuishi, Chisako ^{[2
]}

Kumasaka, Sakae ^{[2
]}

Kondo, Yoichi ^{[3
]}

Takatera, Akihiro ^{[4
]}

Hokuto, Isamu ^{[5
]}

Morioka, Ichiro ^{[6
,15
]}

Ogiwara, Kazutaka ^{[7
]}

Tobita, Kimimasa ^{[7
]}

Takeuchi, Atsuko ^{[8
,49
]}

Nishio, Hisahide ^{[1
,9
]}

Fujioka, Kazumichi ^{[10
]}

Iijima, Kazumoto ^{[10
]}

Takahashi, Akihito ^{[11
]}

Morimoto, Daisaku ^{[12
]}

Washio, Yosuke ^{[12
]}

Takahashi, Yasuhiko ^{[13
]}

Yamamoto, Junko ^{[13
]}

Takahata, Yasushi ^{[14
]}

Nagano, Nobuhiko ^{[15
]}

Nakao, Hideto ^{[16
]}

Yokota, Tomoyuki ^{[16
]}

Yoshimoto, Seiji ^{[16
]}

Ieda, Kuniko ^{[17
]}

Ohno, Norioki ^{[18
]}

Cho, Kazutoshi ^{[19
]}

Shiraishi, Hideaki ^{[19
]}

Koyama, Norihisa ^{[20
]}

Sugimoto, Mari ^{[20
]}

Iwanaga, Manabu ^{[21
]}

Matsuo, Muneaki ^{[21
]}

Osaka, Hitoshi ^{[22
]}

Shimozawa, Hironori ^{[22
]}

Yamagata, Takanori ^{[22
]}

Fukushima, Naoki ^{[23
]}

Ueda, Masaaki ^{[24
]}

Yoshida, Shinobu ^{[25
]}

Shimomura, Hideki ^{[26
]}

Takeshima, Yasuhiro ^{[26
]}

Kinoshita, Fumiko ^{[27
]}

Sato, Tatsuharu ^{[27
]}

Niijima, Shinichi ^{[28
]}

Yoshida, Noboru ^{[28
]}

Masunaga, Ken ^{[29
]}

Aoki, Mikihiro ^{[30
]}

Morisawa, Takeshi ^{[31
]}

Nagayama, Yoshihisa ^{[32
]}

机构：

[1] Kobe Univ, Dept Community Med & Social Healthcare Sci, Div Epidemiol,Grad Sch Med, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

[2] Japanese Red Cross Katsushika Matern Hosp, Katsushika Ku, 5-11-12 Tateishi, Tokyo 1240012, Japan

[3] Matsuyama Red Cross Hosp, 1 Bunkyo Cho, Matsuyama, Ehime 7908524, Japan

[4] Chibune Gen Hosp, Nishiyodogawa Ku, 3-2-39 Fukumachi, Osaka 5550034, Japan

[5] St Marianna Univ, Dept Pediat, Sch Med, 2-16-1 Sugao, Kawasaki, Kanagawa 2168511, Japan

[6] Nihon Univ, Dept Pediat & Child Hlth, Sch Med, Itabashi Ku, 30-1 Oyaguchi Kamicho, Tokyo 1738610, Japan

[7] Biogen Japan Ltd, Chuo Ku, 1-4-1 Nihonbashi, Tokyo 1030027, Japan

[8] Kobe Pharmaceut Univ, Higashinada Ku, 4-19-1 Motoyamakitamachi, Kobe, Hyogo 6588558, Japan

[9] Kobe Gakuin Univ, Fac Rehabil, Dept Occupat Therapy, Nishi Ku, 518 Arise,Ikawadani Cho, Kobe, Hyogo 6512180, Japan

[10] Grad Sch Med, Kobe, Hyogo, Japan

[11] Kurashiki Cent Hosp, Kurashiki, Okayama, Japan

[12] Okayama Univ Hosp, Okayama, Japan

[13] Japan Community Hlth Care Org Kyushu Hosp, Kitakyushu, Fukuoka, Japan

[14] Fukuoka Childrens Hosp, Fukuoka, Fukuoka, Japan

[15] Nihon Univ, Sch Med, Tokyo, Japan

[16] Hyogo Prefectural Kobe Childrens Hosp Perinatal C, Kobe, Hyogo, Japan

[17] Tosei Gen Hosp, Seto, Aichi, Japan

[18] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan

[19] Hokkaido Univ Hosp, Sapporo, Hokkaido, Japan

[20] Toyohashi Municipal Hosp, Toyohashi, Aichi, Japan

[21] Saga Univ, Saga, Japan

[22] Jichi Med Sch, Shimotsuke, Tochigi, Japan

[23] Almeida Mem Hosp, Oita, Japan

[24] Toyooka Hosp, Toyooka, Japan

[25] Omihachiman Community Med Ctr, Omihachiman, Japan

[26] Hyogo Coll Med, Nishinomiya, Hyogo, Japan

[27] Nagasaki Univ Hosp, Nagasaki, Japan

[28] Juntendo Univ, Nerima Hosp, Tokyo, Japan

[29] Tokyo Metropolitan Otsuka Hosp, Tokyo, Japan

[30] Natl Hosp Org Nagasaki Med Ctr, Nagasaki, Japan

[31] Kakogawa Cent City Hosp, Kakogawa, Hyogo, Japan

[32] Niigata City Gen Hosp, Niigata, Japan

[33] Chiba Childrens Hosp, Chiba, Japan

[34] Yokosuka Gen Hosp Uwamachi, Yokosuka, Kanagawa, Japan

[35] Kouseiren Takaoka Hosp, Takaoka, Toyama, Japan

[36] Hokkaido Med Ctr Child Hlth & Rehabil, Sapporo, Hokkaido, Japan

[37] Sapporo Med Univ Hosp, Sapporo, Hokkaido, Japan

[38] Japanese Red Cross Nagoya Daini Hosp, Nagoya, Aichi, Japan

[39] Akita Univ, Grad Sch Med, Akita, Japan

[40] Japanese Red Cross Saitama Hosp, Saitama, Japan

[41] Univ Ryukyus, Grad Sch Med, Nishihara, Okinawa, Japan

[42] Numazu City Hosp, Numazu, Shizuoka, Japan

[43] Sapporo City Gen Hosp, Sapporo, Hokkaido, Japan

[44] Aiiku Hosp, Maternal & Child Hlth Ctr, Tokyo, Japan

[45] Hiroshima City Hiroshima Citizens Hosp, Hiroshima, Japan

[46] Juntendo Univ, Shizuoka Hosp, Tokyo, Japan

[47] Yamaguchi Univ, Ube, Yamaguchi, Japan

[48] Natl Ctr Child Hlth & Dev, Tokyo, Japan

[49] Kobe Pharmaceut Univ, Kobe, Hyogo, Japan

来源：

INTERNATIONAL JOURNAL OF NEONATAL SCREENING | 2019年 / 5卷 / 04期

关键词：

mCOP-PCR; SMN1; SMN2; spinal muscular atrophy; SMN2 COPY NUMBER; NATURAL-HISTORY; SHAM CONTROL; NUSINERSEN; DIAGNOSIS; PCR;

D O I：

10.3390/ijns5040041

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：13

共 30 条

[1] SPINAL MUSCULAR ATROPHY: DIAGNOSIS AND MANAGEMENT IN A NEW THERAPEUTIC ERA [J].

Arnold, W. David ;

Kassar, Darine ;

Kissel, John T. .

MUSCLE & NERVE, 2015, 51 (02) :157-167

[2] Newborn screening for SMA in Southern Belgium [J].

Boemer, Francois ;

Caberg, Jean-Hubert ;

Dideberg, Vinciane ;

Dardenne, Domien ;

Bours, Vincent ;

Hiligsmann, Mickael ;

Dangouloff, Tamara ;

Servais, Laurent .

NEUROMUSCULAR DISORDERS, 2019, 29 (05) :343-349

[3] Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening [J].

Chien, Yin-Hsiu ;

Chiang, Shu-Chuan ;

Weng, Wen-Chin ;

Lee, Ni-Chung ;

Lin, Ching-Jie ;

Hsieh, Wu-Shiun ;

Lee, Wang-Tso ;

Jong, Yuh-Jyh ;

Ko, Tsang-Ming ;

Hwu, Wuh-Liang .

JOURNAL OF PEDIATRICS, 2017, 190 :124-+

[4]

Czibere L., 2019, EUR J HUM GENET, DOI [10.1038/s41431-019-0476-431363188, DOI 10.1038/S41431-019-0476-431363188]

[5] Quantitative analyses of SMN1 and SMN2 based on real-time LightCycler PCR:: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy [J].

Feldkötter, M ;

Schwarzer, V ;

Wirth, R ;

Wienker, TF ;

Wirth, B .

AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (02) :358-368

[6] Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy [J].

Finkel, R. S. ;

Mercuri, E. ;

Darras, B. T. ;

Connolly, A. M. ;

Kuntz, N. L. ;

Kirschner, J. ;

Chiriboga, C. A. ;

Saito, K. ;

Servais, L. ;

Tizzano, E. ;

Topaloglu, H. ;

Tulinius, M. ;

Montes, J. ;

Glanzman, A. M. ;

Bishop, K. ;

Zhong, Z. J. ;

Gheuens, S. ;

Bennett, C. F. ;

Schneider, E. ;

Farwell, W. ;

De Vivo, D. C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (18) :1723-1732

[7] Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study [J].

Finkel, Richard S. ;

Chiriboga, Claudia A. ;

Vajsar, Jiri ;

Day, John W. ;

Montes, Jacqueline ;

De Vivo, Darryl C. ;

Yamashita, Mason ;

Rigo, Frank ;

Hung, Gene ;

Schneider, Eugene ;

Norris, Daniel A. ;

Xia, Shuting ;

Bennett, C. Frank ;

Bishop, Kathie M. .

LANCET, 2016, 388 (10063) :3017-3026

[8]

Finkel RS, 2014, NEUROLOGY, V83, P810, DOI 10.1212/WNL.0000000000000741

[9] DETECTION OF SINGLE DNA-BASE DIFFERENCES BY COMPETITIVE OLIGONUCLEOTIDE PRIMING [J].

GIBBS, RA ;

NGUYEN, PN ;

CASKEY, CT .

NUCLEIC ACIDS RESEARCH, 1989, 17 (07) :2437-2448

[10]

Glascock Jacqueline, 2018, J Neuromuscul Dis, V5, P145, DOI 10.3233/JND-180304

← 1 2 3 →