Natera, Inc., San Carlos, California, USA.
Nephrology and Hypertension Medical Associates, P.C., Beaufort, South Carolina, USA.
Am J Nephrol. 2021;52(8):684-690. doi: 10.1159/000518253. Epub 2021 Sep 2.
Recent literature highlights the clinical utility of genetic testing for patients with kidney disease. Genetic testing provides significant benefits for reproductive risk counseling, including the option of in vitro fertilization with preimplantation genetic testing for monogenic disease (PGT-M). PGT-M allows for a significant reduction in risk for a pregnancy affected with the familial disease. We aim to summarize our experience with PGT-M for genes with kidney involvement as either a primary or secondary feature of the disease.
All PGT-M tests performed by the reference laboratory between September 2010 and July 2020 were reviewed for clinical indication and cases for which the disease tested included a renal component. Each patient referred for PGT-M had an existing molecular genetic diagnosis themselves or in their family. Frequency of each condition, gene, inheritance pattern, and year over year increase in referral cases was analyzed.
In the study cohort, the most common disease targeted was autosomal dominant polycystic kidney disease, caused by pathogenic variants in the PKD1 or PKD2 genes, which accounted for 16.5% (64/389) of cases. The 5 most common referral indications accounted for 51.9% (202/389) of the cases. Autosomal recessive inheritance accounted for 52.0% (26/50) of conditions for which PGT-M was performed. The number of PGT-M tests performed for conditions that included either primary or secondary kidney disease increased from 5 cases in 2010 to 47 cases in the 2020 study period.
DISCUSSION/CONCLUSION: These data suggest that the pursuit of PGT-M by couples at risk for passing on conditions with a kidney component is common and has significantly increased since 2010. With this rising trend of patients undergoing PGT-M and the prerequisite of molecular genetic confirmation in the PGT-M process, this study underscores the importance of the reproductive component to a molecular genetic diagnosis for patients with kidney disease, especially as the accessibility of genetic testing and utilization by nephrologists grows.
最近的文献强调了基因检测在肾病患者中的临床应用。基因检测为生殖风险咨询提供了重要的益处，包括单基因疾病的体外受精前遗传检测（PGT-M）的选择。PGT-M 可以显著降低受家族疾病影响的妊娠风险。我们旨在总结我们在肾脏受累的基因的 PGT-M 经验，这些基因作为疾病的主要或次要特征。
回顾了 2010 年 9 月至 2020 年 7 月参考实验室进行的所有 PGT-M 检测，以了解临床指征以及测试的疾病中包含肾脏成分的情况。每一位接受 PGT-M 检测的患者自己或其家族中都有现有的分子遗传学诊断。分析了每种疾病的频率、基因、遗传模式以及每年转诊病例的增加情况。
在研究队列中，最常见的靶向疾病是常染色体显性多囊肾病，由 PKD1 或 PKD2 基因的致病性变异引起，占 16.5%（64/389）。最常见的 5 种转诊指征占 389 例的 51.9%（202/389）。常染色体隐性遗传占进行 PGT-M 的 52.0%（26/50）疾病。包括主要或次要肾脏疾病的疾病的 PGT-M 检测数量从 2010 年的 5 例增加到 2020 年的 47 例。
讨论/结论：这些数据表明，有肾脏疾病家族史的夫妇寻求进行 PGT-M 的情况很常见，自 2010 年以来显著增加。随着越来越多的患者接受 PGT-M 治疗，以及 PGT-M 过程中对分子遗传学确认的前提要求，本研究强调了生殖因素对肾脏疾病患者分子遗传学诊断的重要性，特别是随着基因检测的普及和肾病医生的应用增加。
