Please wait a minute...
欢迎访问发育医学电子杂志,今天是
发育医学电子杂志  2025, Vol. 13 Issue (5): 330-337    DOI: 10.3969/j.issn.2095-5340.2025.05.002
  围产医学   论著 |新生儿 |
新生儿单基因遗传病基因筛查结果分析及筛查策略的探讨
曾雯   戚红  祝建疆  李小鸥   张巧   蔡莉蓉   雒瑶
(1. 北京市海淀区妇幼保健院 产前诊断科,北京 100094;2. 北京市海淀区妇幼保健院 新生儿科,北京 100094)
Analysis of genetic screening results for monogenic diseases in newborns and exploration of screening strategies
Zeng Wen, Qi Hong , Zhu Jianjiang,et al
 (1. Department of Prenatal Diagnosis, Haidian District Maternal and Child Health Care Hospital, Beijing 100094, China; 
2. Department of Neonatology, Haidian District Maternal and Child Health Care Hospital, Beijing 100094, China)
下载:  PDF (1008KB) 
输出:  BibTeX | EndNote (RIS)      
摘要 【摘要】 目的 分析新生儿单基因遗传病基因筛查的结果,了解本地区致病基因的变异特点,制订适合本地化的新生儿基因筛查策略。 方法 选取 2022 年 7 月至 2024 年 12 月于北京市海淀区妇幼保健院分娩且经监护人知情同意自愿要求接受基因检测的 2 217 例新生儿为研究对象。使用基于目的基因捕获的二代测序(next-generation sequencing,NGS)技术对涉及 542 种疾病亚型的 599 个基因进行检测。对初筛阳性者应用 Sanger 测序、多重连接依赖性探针扩增(multiplex ligation-dependent probe 
amplification,MLPA)、长片段聚合酶链反应(long-range polymerase chain reaction,LR-PCR)等技术进行家系验证。 结果  2 217 例新生儿中,经家系验证后阳性 716 例(32.30%)。其中 UGT1A1 基因阳性 307 例(13.85%),FLG 基因阳性 274 例(12.36%)。经调整策略,将 UGT1A1 基因及 FLG 基因阳性病例中部分临床症状较轻、预后良好病例划归于携带者,不计入阳性病例。经重新统计分析,阳性 146 例(6.59%),隐性基因携带者 1 787 例(80.60%),未发现变异者 284 例(12.81%)。阳性病例中,常染色体显性基因变异 91 例,常染色体隐性基因纯合变异 7 例,复合杂合变异 31 例,X- 连锁显性基因变异 8 例,X-
连锁隐性基因半合子变异 3 例,线粒体基因变异 5 例。阳性率前 5 位基因分别为 FLG(0.50%)、LDLR(0.50%)、APOB(0.32%)、GJB2(0.27%)、G6PD(0.27%)。6 例阳性病例在新生儿期已出现临床表型。变异携带率前 10 位的基因分别为 UGT1A1(49.35%)、FLG(12.36%)、GJB2(10.10%)、CFTR(6.54%)、DUOX2 (5.41%)、ATP7B (3.47%)、CYP21A2(3.07%)、SLC26A4 (2.98%)、PAH(2.93%)和 GALC(2.80%)。结论 基于 NGS 技术的新生儿基因筛查提高了新生儿单基因遗传病的筛查能力,结合家系验证可提供效的指导,实现早发现、早干预的目的。随着数据的积累,不断调整新生儿基因筛查策略,以实现更精、高效的筛查。
服务
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章
关键词:  二代测序  单基因遗传病  新生儿筛查  筛查策略    
Abstract: 【Abstract】 Objective To analyze the results of genetic screening for monogenic disorders, investigate the characteristics of pathogenic genetic variants in the local population, and formulate a locally tailored newborn genetic screening strategy. Method A total of 2 217 newborns deliveredat the Haidian District Maternal and Child Health Care Hospital in Beijingbetween July 2022 and December 2024, whose guardians provided informed consent and voluntary request for genetic testing were enrolled. Targeted gene capture-based next-generation sequencing (NGS) was performed to screen 
599 genes associated with 542 disease subtypes. Initial screen-positive individuals underwent familial verification using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), longrange polymerase chain reaction (LR-PCR), and other techniques. Result Among the 2 217 newborns, 716 cases (32.30%) were identified as positive through familial verification. This included 307 cases (13.85%) with UGT1A1 variants and 274 cases (12.36%) with FLG variants. After applying an adjusted classification strategy, cases with milder symptoms and favorable prognosis associated with UGT1A1 or FLG variants were reclassified as carriers and excluded from the positive case count. After re-analysis, 146 cases (6.59%) 
were positive, 1 787 cases (80.60%) were recessive gene carriers, and 284 cases (12.81%) with no variants detected. Among the positive cases, there were 91 cases of autosomal dominant pathogenic variants, 7 cases of autosomal recessive homozygous variants, 31 cases of compound heterozygous variants, 8 cases of X-linked dominant heterozygous variants, 3 cases of X-linked recessive hemizygous variants, and 5 cases of mitochondrial gene variants. The top five genes by positive rate were FLG (0.50%), LDLR (0.50%), APOB (0.32%), GJB2 (0.27%), and G6PD (0.27%). Six positive cases exhibited clinical phenotypes during the neonatal period. The top ten genes in terms of carrier rates were UGT1A1 (49.35%), FLG (12.36%), 
GJB2 (10.10%), CFTR (6.54%), DUOX2 (5.41%), ATP7B (3.47%), CYP21A2 (3.07%), SLC26A4 (2.98%), PAH(2.93%), and GALC (2.80%). Conclusion NGS based neonatal genetic screening enhances the ability to detect monogenic diseases in newborns. Combined with familial validation, it provides actionable guidance for early identification and intervention. Continuous refinement of strategies for neonatal genetic screening through data accumulation will enable more precise and efficient screening

Key words:  Next-generation sequencing    Monogenic diseases    Newborn screening    Screening strategy
收稿日期:  2025-06-12                     发布日期:  2025-10-01     
基金资助: 海淀区高层次人才项目(2022HDXD004)
通讯作者:  戚红    E-mail:  qihong_2009@sina.com
引用本文:    
曾雯  戚红  祝建疆  李小鸥  张巧  蔡莉蓉  雒瑶. 新生儿单基因遗传病基因筛查结果分析及筛查策略的探讨[J]. 发育医学电子杂志, 2025, 13(5): 330-337.
Zeng Wen, Qi Hong , Zhu Jianjiang, et al. Analysis of genetic screening results for monogenic diseases in newborns and exploration of screening strategies. Journal of Developmental Medicine(Electronic Version), 2025, 13(5): 330-337.
链接本文:  
http://www.fyyxzz.com/CN/10.3969/j.issn.2095-5340.2025.05.002  或          http://www.fyyxzz.com/CN/Y2025/V13/I5/330
[1] 常家祯 戚庆炜 周希亚 蒋宇林 吕嬿 郝娜 李萌萌 阴凯丽 杨雪婷 张晗喆. 单基因遗传病扩展性携带者筛查研究[J]. 发育医学电子杂志, 2025, 13(5): 321-329.
[2] 闫磊  张万巧 张玉佩 陈雨晗 梅亚波. 串联质谱联合气相质谱在新生儿重症监护病房遗传代谢病筛查诊断中的应用价值[J]. 发育医学电子杂志, 2024, 12(1): 7-12.
[3] 张巧 曾雯 祝建疆 戚红. 基因检测在新生儿常见单基因遗传病筛查中的应用[J]. 发育医学电子杂志, 2023, 11(5): 377-383.
[4] 贾立云 封露露 封纪珍 弓苗 马翠霞. 河北省石家庄市新生儿短链酰基辅酶A脱氢酶缺乏症筛查及基因突变分析[J]. 发育医学电子杂志, 2023, 11(1): 14-18.
[5] 王磊 安邦权 黄盛文. 基于母体外周血胎儿游离DNA 的单基因病无创产前诊断研究进展[J]. 发育医学电子杂志, 2023, 11(1): 53-59.
[6] 卢彦平 张鑫悦. 胎儿骨骼发育异常的诊断[J]. 发育医学电子杂志, 2019, 7(4): 252-254.
[7] 潘虹 陈倩. 产前遗传学诊断技术研究进展[J]. 发育医学电子杂志, 2019, 7(3): 168-172.
[8] 杨凤杰 周建华 仇丽茹. LAMB2基因突变致耐药型肾病综合征[J]. 发育医学电子杂志, 2015, 3(3): 152-155.
No Suggested Reading articles found!
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed