BACKGROUND The DICER1 syndrome is a tumor-predisposition disorder caused by germline pathogenic variation in DICER1 and is associated with cystic nephroma and other renal neoplasms. Dicer1 mouse and rare human DICER1 syndrome case reports describe structural kidney and collecting system anomalies. We investigated renal function and the frequency of structural abnormalities of the kidney and collecting system in individuals with germline loss-of-function variants in DICER1. METHODS In this family-based cohort study, prospectively ascertained germline DICER1-mutation carriers (DICER1-carriers) and unaffected family controls were evaluated at the National Institutes of Health Clinical Center with renal ultrasound and comprehensive laboratory testing. Two radiologists reviewed the imaging studies from all participants for structural abnormalities, cysts, and tumors. RESULTS Eighty-nine DICER1-carriers and 61 family controls were studied. Renal cysts were detected in 1/33 DICER1-carrier children without history of cystic nephroma. Similar proportions of adult DICER1-carriers (8/48; 17%) and controls (11/50; 22%) had ultrasound-detected renal cysts (P = 0.504). 8/89 (9%) DICER1-carriers harbored ultrasound-detected structural abnormalities of varying severity within the collecting system or kidney, nephrolithiasis, or nephrocalcinosis. None of the family controls (0/61) had similar findings on ultrasound (P = 0.02). No meaningful differences in renal laboratory values between DICER1-carriers and unaffected family controls were observed. CONCLUSIONS Our report is the first to systematically characterize renal function and anatomy in a large prospective cohort of DICER1-carriers and DICER1-negative family controls. DICER1-carriers may be at increased risk of structural anomalies of the kidney or collecting system. The role for DICER1 in renal morphogenesis merits additional investigation.

中文翻译：

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DICER1综合征中的结构性肾脏异常：一项基于家庭的队列研究。

背景技术DICER1综合征是由DICER1的种系致病性变异引起的肿瘤易感性疾病，并且与囊性肾瘤和其他肾肿瘤有关。Dicer1小鼠和罕见的人类DICER1综合征病例报告描述了肾脏结构和采集系统异常。我们调查了DICER1中具有种系功能丧失变异的个体的肾脏功能以及肾脏和收集系统的结构异常的频率。方法在这项基于家庭的队列研究中，前瞻性确定的种系DICER1突变携带者（DICER1携带者）和未受影响的家庭对照在美国国立卫生研究院临床中心接受了肾脏超声检查和综合实验室测试。两名放射科医生对所有参与者的影像学研究进行了结构异常检查，囊肿和肿瘤。结果研究了89个DICER1携带者和61个家庭对照。在没有囊性肾瘤病史的1/33 DICER1携带者儿童中检测到肾囊肿。成人DICER1携带者（8/48; 17％）和对照组（11/50; 22％）的相似比例具有超声检测到的肾囊肿（P = 0.504）。8/89（9％）DICER1携带者在收集系统或肾脏，肾结石症或肾钙化病中具有超声检测到的严重程度不同的结构异常。没有一个家庭对照（0/61）在超声检查中有类似的发现（P = 0.02）。在DICER1携带者和未受影响的家庭对照之间，在肾脏实验室值方面没有观察到有意义的差异。结论我们的报告是第一个系统性地描述DICER1携带者和DICER1阴性家庭对照的大型前瞻性队列中肾脏功能和解剖特征的研究。DICER1携带者可能面临肾脏或收集系统结构异常的风险增加。DICER1在肾形态发生中的作用值得进一步研究。