Institute for Women's Health, 86-96 Chenies Mews, University College London, London WC1E 6HX, UK.
Department of Obstetrics, Gynaecology and Reproductive Medicine, Hospital Universitário de Santa Maria, Av. Prof. Egas Moniz, 1649-035 Lisbon, Portugal.
Hum Reprod. 2017 Oct 1;32(10):1951-1956. doi: 10.1093/humrep/dex272.
Conventionally, the search for carrier status was based on ethnicity and/or family history and targeted to a restricted number of genetic conditions and mutations. This is now being replaced by extended panels testing for hundreds of genetic disorders with a broad range of phenotypes, in what is called 'expanded carrier screening'. While the ultimate aim of these panels is to increase the reproductive autonomy of the individuals and couples by providing preconception knowledge that could lead to the broadest range of available options, including PGD, we argue that: (i) Given the number and heterogeneity of the conditions included in panels, it cannot be guaranteed that a couple who tests positive for one of those conditions will be eligible for PGD; patients should be informed of this potential limitation before undertaking screening. (ii) Family history is typically lacking in couples identified through panels as being at high-risk for certain disorders. This should promote a reflection on the inclusion of personal experience with a condition as a consideration for PGD in disorders with incomplete penetrance or for which treatment options are available. (iii) With the advent of next-generation sequencing panels, cases of couples in which one member carries a disease-causing variant and the other has a variant of uncertain significance found in the same gene are likely to become more common and need to be discussed from the PGD perspective. (iv) With comprehensive panels where healthy individuals are likely to be identified as carriers for several conditions, testing of carrier status for embryos and prioritisation of the embryos to transfer needs reassessing. We believe that these points should be included in the discussion on expanded carrier screening and that all stakeholders, patients included, must be aware of the challenges and limitations that may come with a positive result.
传统上，携带者检测是基于种族和/或家族史，并针对少数几种遗传疾病和突变进行靶向检测。现在，这种方法正在被更广泛的基因检测所取代，这些检测可以检测数百种遗传疾病，并涵盖广泛的表型，这被称为“扩展携带者筛查”。虽然这些检测的最终目的是通过提供可以导致最广泛的可用选择的孕前知识，包括 PGD，从而提高个体和夫妇的生殖自主权，但我们认为：(i) 鉴于面板中包含的条件数量和异质性，不能保证对其中一种条件检测呈阳性的夫妇有资格进行 PGD；在进行筛查之前，应告知患者这种潜在的局限性。(ii) 在通过面板确定的高危夫妇中，通常缺乏家族病史。这应该促使人们思考将个人对某种疾病的体验纳入不完全外显或有治疗选择的疾病的 PGD 考虑因素。(iii) 随着下一代测序面板的出现，一对夫妇中一方携带致病变异体，另一方携带同一基因中不确定意义的变异体的情况可能会变得更加常见，需要从 PGD 角度进行讨论。(iv) 在涵盖广泛的情况下，健康个体可能被确定为多种疾病的携带者，因此对胚胎进行携带者检测和胚胎转移的优先级需要重新评估。我们认为，这些观点应该纳入扩展携带者筛查的讨论中，所有利益相关者，包括患者，都必须意识到可能会出现阳性结果的挑战和局限性。
