Baylarov Rauf, Senol Ozgur, Atan Merve, Berdeli Afig
Department of Pediatrics, Pediatric Nephrology Division, Azerbaijan State Medical University, Baku, Azerbaijan.
Department of Pediatric Molecular Medicine Laboratory, Ege University Medical Faculty, Izmir, Turkey.
Saudi J Kidney Dis Transpl. 2020 Jan-Feb;31(1):144-149. doi: 10.4103/1319-2442.279934.
Nephrotic syndrome (NS) is characterized by proteinuria in children. Steroid- resistant NS (SRNS) is defined by resistance to standard steroid therapy, and it continues to be one of the most common causes of chronic renal failure. Molecular studies have revealed specialized molecules in different regions of the podocytes that play a role in proteinuria. Mutations in NPHS2 that encode for podocin constitute a frequent cause of SRNS worldwide. This study aimed to screen for podocin mutations in Azerbaijani patients with SRNS. Our study included 21 pediatric patients with SRNS aged between 0 and 18 years and the same number of healthy control groups. Mutational analysis of the NPHS2 gene was performed using direct sequencing methods. Disease-causing mutations in the NPHS2 gene were detected in eight patients (38%). Thirteen patients (62%) had NPHS2 mutations without causing the disease. Two patients had p.Val290Met homozygous mutation; two had p.Arg229Gln homozygous mutations; and one each had p.Pro20Leu homozygote, p.Leu169Pro homozygote, p.Arg138Gln homozygote, and p.Arg168His homozygous mutations. When we correlated the NPHS2 mutation status with disease progression, there was a statistically significant increase in serum creatinine, proteinuria, and serum albumin values in patients with NPHS2 gene mutations compared to the group without mutation (P <0.05). Our study concludes that mutations of the NPHS2 gene (38%) are heterogeneous in Azerbaijani SRNS patients. Based on our results, we support a model in which ethnicity plays an important role in certain NPHS2 mutations. NPHS2 mutation analysis may help to better predict the course of the disease, remove unnecessary long-term immunosuppressive therapy, and develop specific treatment.
肾病综合征（NS）在儿童中以蛋白尿为特征。激素抵抗型肾病综合征（SRNS）的定义是对标准激素治疗耐药，它仍然是慢性肾衰竭最常见的病因之一。分子研究揭示了足细胞不同区域的特定分子在蛋白尿中发挥作用。编码足突蛋白的NPHS2基因突变是全球SRNS的常见病因。本研究旨在筛查阿塞拜疆SRNS患者的足突蛋白基因突变。我们的研究纳入了21例年龄在0至18岁之间的SRNS儿科患者以及相同数量的健康对照组。使用直接测序方法对NPHS2基因进行突变分析。在8例患者（38%）中检测到NPHS2基因的致病突变。13例患者（62%）有NPHS2基因突变但未致病。2例患者有p.Val290Met纯合突变；2例有p.Arg229Gln纯合突变；各有1例患者有p.Pro20Leu纯合子、p.Leu169Pro纯合子、p.Arg138Gln纯合子和p.Arg168His纯合突变。当我们将NPHS2突变状态与疾病进展相关联时，与未突变组相比，NPHS2基因突变患者的血清肌酐、蛋白尿和血清白蛋白值有统计学意义的升高（P<0.05）。我们的研究得出结论，在阿塞拜疆SRNS患者中，NPHS2基因的突变（38%）是异质性的。基于我们的结果，我们支持一种模型，即种族在某些NPHS2突变中起重要作用。NPHS2突变分析可能有助于更好地预测疾病进程，去除不必要的长期免疫抑制治疗，并制定特定的治疗方案。
