Bai Ling, Zhuang Jing, Zhang Changrong, Lu Chen, Tian Xuefei, Jiang Hong
Department of Nephrology and Rheumatology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Division of Nephrology, Department of Internal Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Front Pediatr. 2021 Sep 23;9:692727. doi: 10.3389/fped.2021.692727. eCollection 2021.
Pathogenic variants in the gene encoding podocin in kidney podocytes are associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) by disrupting podocyte function and the integrity of the glomerular filtration barrier. The outcome is generally poor by progressing into end-stage kidney disease (ESKD). With the help of gene diagnostics, we can further understand the role of podocin of podocytes in the development and progression of SRNS. However, the pathological mutation of and clinical relevance remain further elusive. Two siblings, a 15-year-old girl and her 10-year-old younger brother from a consanguineous Chinese family, presented with nephrotic syndrome. Both of them developed progressive proteinuria starting from the 5-year-old of age. The renal pathological lesions for them revealed focal segmental glomerulosclerosis (FSGS). There was no response to the glucocorticoid, calcineurin inhibitors, and rituximab treatment. The female affected patient received the hemodialysis treatment due to ESKD in June 2020; the male patient was still in follow-up presenting with SRNS. The mutational screening of the two patients and their parents using Trio whole-exome sequencing showed the gene missense mutation in exon 5 (A593C), for which the two siblings were homozygous and their parents confirmed heterozygous asymptomatic carriers. No other SRNS-related gene variants with the SRNS were determined. Pathological gene variants screening in children clinically suspected with SRNS might be helpful in the diagnosis as well as appropriate decisions on treatment strategies and prediction of prognosis.
肾足细胞中编码足突蛋白的基因发生致病变异，会破坏足细胞功能和肾小球滤过屏障的完整性，从而与常染色体隐性遗传性类固醇抵抗型肾病综合征（SRNS）相关。其结果通常较差，会进展为终末期肾病（ESKD）。借助基因诊断，我们可以进一步了解足细胞中足突蛋白在SRNS发生发展中的作用。然而，其致病突变和临床相关性仍有待进一步明确。来自一个近亲通婚的中国家庭的两名兄弟姐妹，一名15岁女孩和她10岁的弟弟，患有肾病综合征。他们两人从5岁起就开始出现进行性蛋白尿。他们的肾脏病理病变显示为局灶节段性肾小球硬化（FSGS）。对糖皮质激素、钙调神经磷酸酶抑制剂和利妥昔单抗治疗均无反应。该患病女性患者于2020年6月因ESKD接受了血液透析治疗；男性患者仍在随访中，患有SRNS。使用三联体全外显子测序对这两名患者及其父母进行突变筛查，结果显示在第5外显子存在该基因错义突变（A593C），两名兄弟姐妹为纯合子，其父母为杂合子无症状携带者。未确定其他与SRNS相关的基因变异。对临床疑似SRNS的儿童进行致病基因变异筛查，可能有助于诊断以及对治疗策略的合理决策和预后预测。
