高级检索
国际遗传学杂志
期刊首页
过刊列表
高级检索
稿件发表
• 指南与共识 •
ENGLISH ABSTRACT
综合性携带者筛查关键问题专家共识(2024版)
中国遗传学会遗传诊断分会
上海市遗传学会临床遗传与遗传咨询专委会
作者及单位信息
·
DOI： 10.3760/cma.j.cn231536-20231110-00047
Expert consensus on key issues of comprehensive carrier screening (2024 edition)
Genetics Diagnosis Branch of Chinese Genetic Society
Clinical Genetics and Genetic Counseling Committee of Shanghai Society of Genetics
Lu Daru
An Yu
Shen Yiping
Authors Info & Affiliations
Genetics Diagnosis Branch of Chinese Genetic Society
Clinical Genetics and Genetic Counseling Committee of Shanghai Society of Genetics
Lu Daru
NHC Key Laboratory of Birth Defects and Reproductive Health/Chongqing Population and Family Planning, Science and Technology Research Institute, Chongqing 401120, China, MOE Engineering Research Center of Gene Technology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200433, China
An Yu
Human Phenome Institute, Fudan University, Shanghai 201203, China
Shen Yiping
Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
·
DOI： 10.3760/cma.j.cn231536-20231110-00047
18383
1141
0
5
25
37
PDF下载
APP内阅读
摘要

综合性携带者筛查是一项针对没有明显遗传病表型，但可能携带遗传病基因致病变异的个体进行的筛查性检测。与常规携带者筛查的区别是，综合性携带者筛查的疾病不仅包括隐性遗传病，也包括具有临床干预意义的成年显性遗传病。综合性携带者筛查旨在提前发现中度及以上严重程度遗传病的生育高风险夫妻和患病高风险个体，为遗传咨询、生殖决策、疾病预防和管理提供依据，减少由遗传病带来的家庭和社会经济负担，提高人群健康水平。目前，携带者筛查相关指南和共识主要涉及常染色体隐性和X连锁遗传病。为介绍和规范综合性携带者筛查的应用，中国遗传学会遗传诊断分会和上海市遗传学会临床遗传与遗传咨询专委会组织部分专家，结合国内外最新进展，制定本共识。共识讨论了综合性携带者筛查的定义和目的、适用人群、筛查基因和疾病的选择原则、筛查策略、报告原则和遗传咨询等关键问题，供政策制定者、临床工作者、检测机构和民众参考。

综合性携带者筛查;显性遗传病;隐性遗传病;专家共识
ABSTRACT

Comprehensive carrier screening (CCS) is a screening test performed on individuals without overt phenotype for genetic disorders but who might have pathogenic variants in disease genes. Currently existing guidelines and consensus for carrier screening mainly focus on autosomal recessive and X-linked genetic disorders, CCS expands its scope beyond these conditions to include dominant conditions with clinical actionability in adulthood. Thus, the goal of CCS is to proactively identify not only at-risk couples of having offspring with moderate to profound genetic disorders, but also at-risk individuals being affected by these disorders. Therefore, CCS serves as a more comprehensive basis for genetic counseling, reproductive decision-making, disease prevention and management, which in turn can better serve the purpose of reducing the familial and socio-economic burdens associated with genetic disorders and improving the overall health of general population. To introduce and standardize the implementation of CCS, the Genetics Diagnosis Branch of Chinese Genetic Society and the Clinical Genetics and Genetic Counseling Committee of Shanghai Society of Genetics organized an expert panel to develop this consensus. The consensus covers key issues related to CCS, including its definition and purpose, the target population, criteria for designing screening panel, screening strategies, reporting guidelines, and genetic counseling. This consensus serves as a reference for policymakers, healthcare professionals, laboratory geneticists, and the general public.

Comprehensive carrier screening;Dominant genetic disorder;Recessive genetic disorder;Expert consensus
Lu Daru, NHC Key Laboratory of Birth Defects and Reproductive Health/Chongqing Population and Family Planning, Science and Technology Research Institute, Chongqing 401120, China, MOE Engineering Research Center of Gene Technology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200433, China, Email: nc.defudabe.nadufulrd
An Yu, Human Phenome Institute, Fudan University, Shanghai 201203, China, Email: nc.defudabe.nadufuyna
Shen Yiping, Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA, Email: udedef.dabravrah.snerdlihcnehs.gnipiy
Copyright by Chinese Medical Association
No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.
All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.
引用本文

中国遗传学会遗传诊断分会,上海市遗传学会临床遗传与遗传咨询专委会. 综合性携带者筛查关键问题专家共识(2024版)[J]. 国际遗传学杂志,2024,47(01)：1-11.

DOI:10.3760/cma.j.cn231536-20231110-00047

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价
本文评分
4.67分 [累计3个]

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

遗传病是遗传物质改变所导致的疾病，是罕见病、部分常见病和出生缺陷的重要病因。罕见病累积患病率估计为3.5%～5.9% [ 1 ]，其中约80%由遗传因素导致；人群中1%～3%的个体是肿瘤和心血管疾病等常见疾病的显性致病变异携带者 [ 2 , 3 , 4 , 5 ]。目前大多数遗传病缺乏治愈方法。然而，通过携带者筛查提前发现可能生育遗传病患儿的高风险夫妻(at-risk couple，ARC)和遗传病患病高风险个体，可以为遗传咨询、生殖决策、疾病预防和管理提供依据，减少由遗传病带来的家庭和社会经济负担，提高人群健康水平。
携带者筛查(carrier screening)始于对Tay-Sachs病、镰状细胞病、囊性纤维化和脊髓性肌萎缩症等个别族裔高发疾病或多种族个别病种提供筛查。随着二代测序(next generation sequencing，NGS)技术的发展和检测成本的下降，携带者筛查拓展到筛查几十到几百种疾病的扩展性携带者筛查(expanded carrier screening) [ 6 ]。由于对"扩展性携带者筛查"的定义较难统一，2021年美国医学遗传学和基因组学会(American College of Medical Genetics and Genomics，ACMG)建议重新使用"携带者筛查"替代"扩展性携带者筛查"的概念 [ 7 ]。尽管过去50余年来，携带者筛查的概念和筛查病种的数量不断发生变化，但既往携带者筛查的疾病主要集中于常染色体隐性和X连锁遗传病，其目的主要用于评估个人或夫妻生育常染色体隐性或X连锁遗传病患儿的风险，从而在孕前或孕期作出生殖决策。随着基因组医学的发展，携带者筛查已拓展到人群基因组筛查(population genomic screening)，不仅可以评估夫妻生育遗传病患儿或流产等风险 [ 8 ]，还可以预测个体患成年疾病的风险 [ 9 ]，从而帮助家庭改善妊娠结局、做出生殖决策，并通过健康管理和疾病预防，降低个体患病风险。
目前，关于携带者筛查的指南和共识主要关注常染色体隐性和X连锁遗传病，对于同时涵盖常染色体显性遗传病的综合性携带者筛查，尚无明确共识。因此，中国遗传学会遗传诊断分会和上海市遗传学会临床遗传与遗传咨询专委会组织了综合性携带者筛查关键问题专家共识的编写工作，目的是更好地发挥综合性携带者筛查在遗传病预防中的作用，为临床应用和遗传咨询提供参考。任何共识都有时效性，期待综合性携带者筛查在临床应用中不断完善。
试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Nguengang Wakap S , Lambert DM , Olry A ,et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database[J]. Eur J Hum Genet, 2020,28(2):165-173. DOI: 10.1038/s41431-019-0508-0 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Murray MF , Evans JP , Khoury MJ . DNA-based population screening: potential suitability and important knowledge gaps[J]. JAMA, 2020,323(4):307-308. DOI: 10.1001/jama.2019.18640 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Murray MF , Khoury MJ , Abul-Husn NS . Addressing the routine failure to clinically identify monogenic cases of common disease[J]. Genome Med, 2022,14(1):10. DOI: 10.1186/s13073-022-01062-6 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Van Hout CV , Tachmazidou I , Backman JD ,et al. Exome sequencing and characterization of 49，960 individuals in the UK Biobank[J]. Nature, 2020,586(7831):749-756. DOI: 10.1038/s41586-020-2853-0 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Gordon AS , Zouk H , Venner E ,et al. Frequency of genomic secondary findings among 21，915 eMERGE network participants[J]. Genet Med, 2020,22(9):1470-1477. DOI: 10.1038/s41436-020-0810-9 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Grody WW , Thompson BH , Gregg AR ,et al. ACMG position statement on prenatal/preconception expanded carrier screening[J]. Genet Med, 2013,15(6):482-483. DOI: 10.1038/gim.2013.47 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Gregg AR , Aarabi M , Klugman S ,et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2021,23(10):1793-1806. DOI: 10.1038/s41436-021-01203-z .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Aminbeidokhti M , Qu JH , Belur S ,et al. Preconception genetic carrier screening for miscarriage risk assessment: A bioinformatic approach to identifying candidate lethal genes and variants[A]. medRxiv, 2023. DOI: 10.1101/2023.05.25.23290518 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Grzymski JJ , Elhanan G , Morales Rosado JA ,et al. Population genetic screening efficiently identifies carriers of autosomal dominant diseases[J]. Nat Med, 2020,26(8):1235-1239. DOI: 10.1038/s41591-020-0982-5 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Committee Opinion No. 691 Summary: Carrier Screening for Genetic Conditions[J]. Obstet Gynecol, 2017,129(3):597-599. DOI: 10.1097/AOG.0000000000001948 .
返回引文位置
[11]
Edwards JG , Feldman G , Goldberg J ,et al. Expanded carrier screening in reproductive medicine-points to consider[J]. Obstet Gynecol, 2015,125(3):653-662. DOI: 10.1097/AOG.0000000000000666 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Murray MF , Giovanni MA , Doyle DL ,et al. DNA-based screening and population health: a points to consider statement for programs and sponsoring organizations from the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2021,23(6):989-995. DOI: 10.1038/s41436-020-01082-w .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Sallevelt SCEH , Stegmann APA , de Koning B ,et al. Diagnostic exome-based preconception carrier testing in consanguineous couples: results from the first 100 couples in clinical practice[J]. Genet Med, 2021,23(6):1125-1136. DOI: 10.1038/s41436-021-01116-x .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Thaxton C , Good ME , DiStefano MT ,et al. Utilizing ClinGen gene-disease validity and dosage sensitivity curations to inform variant classification[J]. Hum Mutat, 2022,43(8):1031-1040. DOI: 10.1002/humu.24291 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Lazarin GA , Hawthorne F , Collins NS ,et al. Systematic classification of disease severity for evaluation of expanded carrier screening panels[J]. PLoS One, 2014,9(12):e114391. DOI: 10.1371/journal.pone.0114391 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Arjunan A , Bellerose H , Torres R ,et al. Evaluation and classification of severity for 176 genes on an expanded carrier screening panel[J]. Prenat Diagn, 2020,40(10):1246-1257. DOI: 10.1002/pd.5762 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Haque IS , Lazarin GA , Kang HP ,et al. A data-driven evaluation of the size and content of expanded carrier screening panels[J]. Genet Med, 2019,21(9):1931-1939. DOI: 10.1038/s41436-019-0466-5 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Guo MH , Gregg AR . Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels[J]. Genet Med Off J Am Coll Med Genet, 2019,21(9):1940-1947. DOI: 10.1038/s41436-019-0472-7 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Lazarin GA , Haque IS , Nazareth S ,et al. An empirical estimate of carrier frequencies for 400＋ causal Mendelian variants: results from an ethnically diverse clinical sample of 23，453 individuals[J]. Genet Med, 2013,15(3):178-186. DOI: 10.1038/gim.2012.114 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Hunter JE , Irving SA , Biesecker LG ,et al. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation[J]. Genet Med, 2016,18(12):1258-1268. DOI: 10.1038/gim.2016.40 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Webber EM , Hunter JE , Biesecker LG ,et al. Evidence-based assessments of clinical actionability in the context of secondary findings: Updates from ClinGen’s Actionability Working Group[J]. Hum Mutat, 2018,39(11):1677-1685. DOI: 10.1002/humu.23631 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Miller DT , Lee K , Abul-Husn NS ,et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2023,25(8):100866. DOI: 10.1016/j.gim.2023.100866 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Simone L , Khan S , Ciarlariello M ,et al. Reproductive male partner testing when the female is identified to be a genetic disease carrier[J]. Prenat Diagn, 2021,41(1):21-27. DOI: 10.1002/pd.5824 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Richards S , Aziz N , Bale S ,et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015,17(5):405-424. DOI: 10.1038/gim.2015.30 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Zhang J , Yao Y , He H ,et al. Clinical interpretation of sequence variants[J]. Curr Protoc Hum Genet, 2020,106(1):e98. DOI: 10.1002/cphg.98 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Tavtigian SV , Greenblatt MS , Harrison SM ,et al. Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework[J]. Genet Med, 2018,20(9):1054-1060. DOI: 10.1038/gim.2017.210 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Tavtigian SV , Harrison SM , Boucher KM ,et al. Fitting a naturally scaled point system to the ACMG/AMP variant classification guidelines[J]. Hum Mutat, 2020,41(10):1734-1737. DOI: 10.1002/humu.24088 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Chen Y . Biallelic p．V37I variant in GJB2 is associated with increasing incidence of hearing loss with age[J]. Genet Med, 2022,24(4):915-923. DOI: 10.1016/j.gim.2021.12.007 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Shen J , Oza AM , del Castillo I ,et al. Consensus interpretation of the p．Met34Thr and p．Val37Ile variants in GJB2 by the ClinGen hearing loss expert panel[J]. Genet Med, 2019,21(11):2442-2452. DOI: 10.1038/s41436-019-0535-9 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Sviderskaya EV , Bennett DC , Ho L ,et al. Complementation of hypopigmentation in p-mutant (Pink-Eyed Dilution) mouse melanocytes by normal human P cDNA, and defective complementation by OCA2 mutant sequences[J]. J Invest Dermatol, 1997,108(1):30-34. DOI: 10.1111/1523-1747.ep12285621 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Suzuki T , Miyamura Y , Tomita Y . High frequency of the Ala481Thr mutation of the P gene in the Japanese population[J]. Am J Med Genet, 2003,118A(4):402-403. DOI: 10.1002/ajmg.a.20044 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Practice Committee and Genetic Counseling Professional Group of the American Society for Reproductive Medicine,American Society for Reproductive Medicine. Indications and management of preimplantation genetic testing for monogenic conditions: a committee opinion[J]. Fertil Steril, 2023,120(1):61-71. DOI: 10.1016/j.fertnstert.2023.03.003 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
den Dunnen JT , Dalgleish R , Maglott DR ,et al. HGVS recommendations for the description of sequence variants: 2016 update[J]. Hum Mutat, 2016,37(6):564-569. DOI: 10.1002/humu.22981 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Restrepo-Cordoba MA , Wahbi K , Florian AR ,et al. Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy[J]. Eur J Heart Fail, 2021,23(8):1276-1286. DOI: 10.1002/ejhf.2250 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Allen EG , Charen K , Hipp HS ,et al. Refining the risk for fragile X-associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size[J]. Genet Med, 2021,23(9):1648-1655. DOI: 10.1038/s41436-021-01177-y .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Smirnov DA , Cheung VG . ATM gene mutations result in both recessive and dominant expression phenotypes of genes and microRNAs[J]. Am J Hum Genet, 2008,83(2):243-253. DOI: 10.1016/j.ajhg.2008.07.003 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Tomlinson IPM . Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer[J]. Nat Genet, 2002,30(4):406-410. DOI: 10.1038/ng849 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Committee Opinion No. 690 Summary: Carrier screening in the age of genomic medicine[J]. Obstet Gynecol, 2017,129(3):595-596. DOI: 10.1097/AOG.0000000000001947 .
返回引文位置
备注信息
A
卢大儒，重庆市人口和计划生育科学技术研究院/国家卫生健康委出生缺陷与生殖健康重点实验室，重庆　401120，复旦大学附属妇产科医院/基因技术教育部工程研究中心，上海　200433，Email： nc.defudabe.nadufulrd
B
安宇，复旦大学人类表型组研究院，上海　201203，Email： nc.defudabe.nadufuyna
C
沈亦平，哈佛医学院波士顿儿童医院遗传与基因组部，美国波士顿　02115，Email： udedef.dabravrah.snerdlihcnehs.gnipiy
D
所有作者声明不存在利益冲突
E
国家重点研发专项课题 (2023YFC2705602)
国家自然科学基金 (82071276)
重庆市自然科学基金重点项目 (cstc2020jcyj-zdxmX0011)
评论 （0条）
注册
登录
时间排序
暂无评论，发表第一条评论抢沙发
最新推荐
更多
乳腺癌内分泌治疗专家共识（2023版）
张少华 等
中华医学杂志 2023,103(38)
高度近视防控专家共识（2023）
中华医学会眼科学分会眼视光学组 等
中华眼视光学与视觉科学杂志 2023,25(06)
中国居民肥胖防治专家共识
中国营养学会肥胖防控分会 等
中华流行病学杂志 2022,43(05)
能量CT临床应用中国专家共识
中华医学会放射学分会 等
中华放射学杂志 2022,56(05)
MedAI助手（体验版）
文档即答
智问智答
机器翻译
回答内容由人工智能生成，我社无法保证其准确性和完整性，该生成内容不代表我们的态度或观点，仅供参考。
生成快照
文献快照

你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持：

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号
小中大