The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists.
The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists.
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DOI：
10.1136/jmedgenet-2015-103144
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发表时间：
2015-07
影响因子：
4
通讯作者：
Canadian College of Medical Geneticists
中科院分区：
文献类型：
--
作者：
Boycott K;Hartley T;Adam S;Bernier F;Chong K;Fernandez BA;Friedman JM;Geraghty MT;Hume S;Knoppers BM;Laberge AM;Majewski J;Mendoza-Londono R;Meyn MS;Michaud JL;Nelson TN;Richer J;Sadikovic B;Skidmore DL;Stockley T;Taylor S;van Karnebeek C;Zawati MH;Lauzon J;Armour CM;Canadian College of Medical Geneticists
本立场声明的目的是向加拿大医学遗传学家、临床实验室遗传学家、遗传咨询师和其他医生提供关于在临床遗传诊断中使用生殖系DNA全基因组测序的建议。制定本声明是为了促进加拿大单基因疾病遗传诊断的临床全基因组测序最佳做法的临床转化和发展；它不涉及该技术在其他领域的临床应用，如癌症的分子研究或健康个体的人群筛查。由医学遗传学家、临床实验室遗传学家、遗传咨询师、伦理学家、律师和遗传研究人员组成的两个多学科小组聚集在一起，审查单基因疾病临床遗传诊断全基因组测序的现有文献和准则，并提出与加拿大情况有关的建议。该声明已分发给加拿大医学遗传学家学院（CCMG）全体成员征求意见，并在纳入反馈意见后，由CCMG董事会批准。CCMG是一个加拿大组织，负责认证医学遗传学家和临床实验室遗传学家，并为加拿大的临床遗传学服务建立专业和道德标准。建议包括：(1)临床全基因组测序是一种适当的诊断评估方法，用于怀疑患有与高度遗传异质性相关的重大单基因疾病的患者，或特定基因检测未能提供诊断的患者；(2)在确定报告偶然发现的益处之前，我们不支持除与主要适应症相关的基因外的疾病相关基因的故意临床分析；(3)临床医生在进行临床全基因组测序前应提供遗传咨询并获得知情同意。咨询应包括讨论检测的局限性，诊断和偶然发现的可能性和含义，以及可能需要进一步分析以促进临床解释，包括在研究环境中进行的研究。随着临床全基因组测序的诊断知识和临床应用的提高，这些建议将被常规地重新评估。虽然该文件是为指导加拿大的实践而编写的，但该声明的适用性更为广泛，并将引起国际临床医生和卫生管辖区的兴趣。
The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally.