Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening

被引：34

作者：

Chen, Ting ^{[3
]}

Fan, Chunna ^{[4
,12
,13
]}

Huang, Yonglan ^{[5
]}

Feng, Jizhen ^{[6
]}

Zhang, Yinhong ^{[7
]}

Miao, Jingkun ^{[8
]}

Wang, Xiaohua ^{[9
]}

Li, Yulin ^{[10
]}

Huang, Cidan ^{[11
]}

Jin, Weiwei ^{[4
,12
]}

Tang, Chengfang ^{[5
]}

Feng, Lulu ^{[6
]}

Yin, Yifan ^{[8
]}

Zhu, Bo ^{[9
]}

Sun, Meng ^{[10
]}

Liu, Xiulian ^{[11
]}

Xiang, Jiale ^{[4
]}

Tan, Minyi ^{[5
]}

Jia, Liyun ^{[6
]}

Chen, Lei ^{[4
]}

Huang, Hui ^{[4
]}

Peng, Huanhuan ^{[4
]}

Sun, Xin ^{[3
]}

Gu, Xuefan ^{[3
]}

Peng, Zhiyu ^{[4
]}

Zhu, Baosheng ^{[7
]}

Zou, Hui ^{[2
,10
]}

Han, Lianshu ^{[1
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Shanghai Inst Pediat Res, Dept Pediat Endocrinol & Genet Metab,Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

[2] Shandong First Med Univ, Neonatal Dis Screening Ctr, Jinan Matern & Child Hlth Hosp, 2 Jianguo Xiaojingsan Rd, Jinan 250001, Peoples R China

[3] Shanghai Jiao Tong Univ, Dept Pediat Endocrinol & Genet Metab, Xinhua Hosp, Shanghai Inst Pediat Res,Sch Med, Shanghai 200092, Peoples R China

[4] BGI Genom, BGI Shenzhen, Shenzhen, Peoples R China

[5] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou Newborn Screening Ctr, Guangzhou, Guangdong, Peoples R China

[6] Shijiazhuang Maternal & Child Hlth Hosp, Dept Genet, Shijiazhuang, Hebei, Peoples R China

[7] Kunming Univ Sci & Technol, Peoples Hosp Yunnan Prov 1, Dept Med Genet, NHC Key Lab Preconcept Hlth Birth Western China,Af, Kunming, Yunnan, Peoples R China

[8] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Pediat, Chongqing, Peoples R China

[9] Inner Mongolia Matern & Child Hlth Care Hosp, Dept Neonatol, Hohhot, Inner Mongolia, Peoples R China

[10] Shandong First Med Univ, Neonatal Dis Screening Ctr, Jinan Matern & Child Care Hosp, Jinan, Peoples R China

[11] Hainan Newborn Screening Ctr, Hainan Women & Childrens Med Ctr, Haikou, Hainan, Peoples R China

[12] Tianjin Med Lab, BGI Tianjin, BGI Shenzhen, Tianjin, Peoples R China

[13] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China

来源：

JAMA NETWORK OPEN | 2023年 / 6卷 / 09期

关键词：

DISORDERS; ASSOCIATION; VARIANTS; CHINA;

D O I：

10.1001/jamanetworkopen.2023.31162

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IMPORTANCE Newborn screening via biochemical tests is in use worldwide. The availability of genetic sequencing has allowed rapid screening for a substantial number of monogenic disorders. However, the outcomes of this strategy have not been evaluated in a general newborn population. OBJECTIVE To evaluate the outcomes of applying gene panel sequencing as a first-tier newborn screening test.DESIGN, SETTING, AND PARTICIPANTS This cohort study included newborns who were prospectively recruited from 8 screening centers in China between February 21 and December 31, 2021. Neonates with positive results were followed up before July 5, 2022. EXPOSURES All participants were concurrently screened using dried blood spots. The screen consisted of biochemical screening tests and a targeted gene panel sequencing test for 128 conditions. The biochemical and genomic tests could both detect 43 of the conditions, whereas the other 85 conditions were screened solely by the gene panel.MAIN OUTCOMES AND MEASURES The primary outcomes were the number of patients detected by gene panel sequencing but undetected by the biochemical test.RESULTS This study prospectively recruited 29 601 newborns (15 357 [51.2%] male). The mean (SD) gestational age was 39.0 (1.5) weeks, and the mean (SD) birth weight was 3273 (457) g. The gene panel sequencing screened 813 infants (2.7%; 95% CI, 2.6%-2.9%) as positive. By the date of follow-up, 402 infants (1.4%; 95% CI, 1.2%-1.5%) had been diagnosed, indicating the positive predictive value was 50.4% (95% CI, 50.0%-53.9%). The gene panel sequencing identified 59 patients undetected by biochemical tests, including 20 patients affected by biochemically and genetically screened disorders and 39 patients affected by solely genetically screened disorders, which translates into 1 out of every 500 newborns (95% CI, v385-v625) benefiting from the implementation of gene panels as a first-tier screening test.CONCLUSIONS AND RELEVANCE In this cohort study, the use of gene panel sequencing in a general newborn population as a first-tier screening test improved the detection capability of traditional screening, providing an evidence-based suggestion that it could be considered as a crucial method for first-tier screening.

引用

页数：12

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