This study aimed to use whole-exome sequencing (WES) to diagnose ultra-rare renal diseases and the clinical impact of such an approach on patient care. Clinical, radiological, pathological, and genetic findings were reviewed in the patients and their family members. Nine patients from nine unrelated Korean families were included in the study and evaluated. WES identified eight different conditions in these patients, i.e., autosomal dominant tubulointerstitial kidney disease associated with UMOD mutation; recurrent urinary stones associated with APRT deficiency; Ayme-Gripp syndrome associated with MAF mutation; short rib-thoracic dysplasia associated with IFT140 mutation; renal coloboma syndrome associated with PAX2 mutations; idiopathic infantile hypercalcemia associated with CYP24A1 mutation; and hypomagnesemia associated with TRPM mutation. Eleven different mutations, including seven novel mutations, were identified, i.e., four truncating mutations, six missense mutations, and one splice-acceptor variant. After genetic confirmation, strategies for the management of the following: medications, donor selection for renal transplantation, and surveillance for extra-renal manifestations were altered. In addition, genetic counseling was provided for the patients and their family members with respect to family member screening for affected but yet unidentified patients and future reproductive planning. As WES can effectively identify ultra-rare genetic renal diseases, facilitate the diagnosis process, and improve patient care, it is a good approach to enable a better understanding of ultra-rare conditions and for the establishment of appropriate counseling, surveillance, and management strategies.

中文翻译：

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通过全外显子组测序诊断的极其罕见的肾脏疾病：在诊断和管理中的实用性


本研究旨在利用全外显子组测序（WES）来诊断极其罕见的肾脏疾病以及这种方法对患者护理的临床影响。对患者及其家人的临床、放射学、病理学和遗传学发现进行了审查。来自九个无关韩国家庭的九名患者被纳入研究并进行评估。 WES 在这些患者中发现了八种不同的病症，即与 UMOD 突变相关的常染色体显性肾小管间质性肾病；与 APRT 缺乏相关的复发性尿结石；与 MAF 突变相关的 Ayme-Gripp 综合征；与 IFT140 突变相关的短肋胸发育不良；与 PAX2 突变相关的肾缺损综合征；与 CYP24A1 突变相关的特发性婴儿高钙血症；以及与 TRPM 突变相关的低镁血症。鉴定了十一种不同的突变，包括七种新突变，即四种截短突变、六种错义突变和一种剪接受体变体。基因确认后，以下管理策略发生改变：药物、肾移植供者选择以及肾外表现监测。此外，还为患者及其家人提供遗传咨询，包括对受影响但身份不明的患者进行家庭成员筛查以及未来的生育计划。由于 WES 可以有效识别超罕见遗传性肾病、促进诊断过程并改善患者护理，因此它是更好地了解超罕见疾病并建立适当的咨询、监测和管理策略的好方法。