Genetic analysis of a child with atypical Hemolytic uremic syndrome and nephrotic-level proteinuria
王大海 1单春荣 2高婷婷 1柳佳 1张冉冉 1张秋业 1常红 1林毅 1梁程红
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作者信息
1. 1青岛大学附属医院儿童肾脏风湿免疫科，青岛 266003
2. 2青岛市妇女儿童医院急诊科，青岛 266034
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摘要
目的 分析1例非典型溶血尿毒综合征(aHUS)伴肾病水平蛋白尿患儿的临床和基因变异特征，以明确其诊断和遗传学病因。 方法 选取2020年6月25日于青岛大学附属医院就诊的1例aHUS伴肾病水平蛋白尿患儿为研究对象。收集患儿的临床资料，应用全外显子组测序(WES)技术对患儿进行基因检测，用Sanger测序进行患儿及其父母的变异位点验证。 结果 患儿为8月龄男性，主要表现为水肿、少尿、血尿、肾病水平蛋白尿、贫血、血小板减低、肌酐及尿素升高、高胆固醇血症，补体水平正常。检测发现患儿携带父源性DGKE基因c.12_18dupGAGGCGG(p.P7fs*37)和母源性c.1042G>T(p.D348Y)复合杂合变异，根据美国医学遗传学与基因组学学会(ACMG)指南，分别评估为可能致病性变异和临床意义不明变异。结合临床表现和基因检测的结果，确诊患儿为aHUS伴肾病水平蛋白尿。 结论 婴幼儿期起病的aHUS伴肾病水平蛋白尿，需考虑DGKE基因变异的可能。本研究确诊了1例aHUS伴肾病水平蛋白尿患儿，明确了其遗传学病因，并拓展了DGKE基因的变异谱。 Objective To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. Methods A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. Results The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c. 12_18dupGAGGCGG (p.P7fs*37) and c. 1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. Conclusion For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
Abstract
Objective To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. Methods A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. Results The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c. 12_18dupGAGGCGG (p.P7fs*37) and c. 1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. Conclusion For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
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