Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju, Korea.
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.
Hematology. 2022 Dec;27(1):603-608. doi: 10.1080/16078454.2022.2075121.
Atypical hemolytic uremic syndrome (aHUS) is characterized by a triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure resulting from platelet thrombi in the microcirculation of the kidney and other organs, in the absence of a preceding diarrheal illness. This report describes a case in which copy number variation (CNV) analysis using next-generation sequencing (NGS) identified the 3/1 deletion in a patient with aHUS.
A 49-year-old Korean female was diagnosed with aHUS based on clinical findings, including schistocytes in peripheral blood and marked thrombocytopenia, suggesting the presence of thrombotic microangiopathy, elevated serum lactate dehydrogenase, and acute kidney injury. Sequence variants and CNV generated from NGS data were estimated to determine if there was a potential genetic cause. Multiplex ligation-dependent probe amplification (MLPA) was conducted to confirm the / deletion identified by NGS with CNV analysis.
No known or novel pathogenic single nucleotide variant or small insertion/deletion that would be predicted to have damaging effects that could lead to aHUS were identified. However, CNV analysis of NGS data identified the heterozygous / deletion. MLPA confirmed this loss of one copy number between the and the genes on chromosome 1q31.3.
We genetically diagnosed a Korean woman harboring a heterozygous / deletion of a known causative gene for aHUS. Our report emphasizes the need for CNV analysis of NGS data and gene dosage assays, such as MLPA, to evaluate large-scale deletions or duplications and generate hybrid genes in patients with suspected aHUS.
非典型溶血尿毒综合征（aHUS）的特征是血小板血栓形成于肾脏和其他器官的微循环中，导致血小板减少、微血管病性溶血性贫血和急性肾衰竭三联征，而无先前的腹泻病。本报告描述了一例使用下一代测序（NGS）进行拷贝数变异（CNV）分析鉴定出 aHUS 患者存在 3/1 缺失的病例。
一名 49 岁的韩国女性根据临床发现被诊断为 aHUS，包括外周血中的破碎红细胞和明显的血小板减少，提示存在血栓性微血管病、血清乳酸脱氢酶升高和急性肾损伤。从 NGS 数据中估计序列变异和 CNV，以确定是否存在潜在的遗传原因。进行多重连接依赖性探针扩增（MLPA）以确认 NGS 与 CNV 分析鉴定的 / 缺失。
未发现已知或新的致病性单核苷酸变异或小插入/缺失，这些变异或缺失预计会产生有害影响，导致 aHUS。然而，NGS 数据的 CNV 分析鉴定出杂合性 / 缺失。MLPA 证实了 1q31.3 染色体上和 基因之间的一个拷贝数缺失。
我们对一名携带 aHUS 已知致病基因杂合性 / 缺失的韩国女性进行了基因诊断。我们的报告强调了需要对 NGS 数据进行 CNV 分析和基因剂量测定，如 MLPA，以评估疑似 aHUS 患者的大片段缺失或重复，并产生杂交 基因。
