Background

Nephrotic syndrome appears as a group of symptoms like proteinuria, edema and hyperlipidemia. Identification of monogenic forms revealed the physiology and pathogenesis of the SRNS.

Methods and Results

We performed Illumina panel sequencing of seven genes in 90 Indian patients to determine the role of these genetic mutations in nephrotic syndrome prognosis. Samtool was used for variants calling, and SnpEff and Snpsift did variants annotation. Clinical significance and variant classification were performed by the ClinVar database. In SSNS and SRNS patients, we found 0.78% pathogenic and 3.41% likely pathogenic mutations. Pathogenic mutations were found in LAMB2, LMX1B and WT1 genes, while likely pathogenic mutations were found in (6/13) LAMB2, (2/13) LMX1B, (2/13) TRPC6, (2/13) PTPRO and (1/13) PMM2 genes. Approximately 46% likely pathogenic mutations were contributed to the LAMB2 gene in SSNS and SRNS patients. We also detect 30 VUS (variants of uncertain significance), which were found (17/30) pathogenic and (13/30) likely pathogenic by different prediction tools.

Conclusions

Multigene panels were used for genetic screening of heterogeneous disorders like nephrotic syndrome in the Indian population. We found pathogenic, likely pathogenic and certain VUS, which were responsible for the pathogenesis of the disease. Therefore, mutational analysis of SSNS and SRNS is necessary to avoid adverse effects of corticosteroids, modify the intensity of immunosuppressing agents, and prevent the disease’s progression.

中文翻译：

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与类固醇抵抗性肾病综合征相关的 TRPC6、WT1、LMX1B、APOL1、PTPRO、PMM2、LAMB2 和 WT1 基因的突变景观

背景

肾病综合征表现为一组症状，如蛋白尿、水肿和高脂血症。单基因形式的鉴定揭示了 SRNS 的生理学和发病机制。

方法和结果

我们对 90 名印度患者的 7 个基因进行了 Illumina 面板测序，以确定这些基因突变在肾病综合征预后中的作用。Samtool 用于变体调用，SnpEff 和 Snpsift 进行变体注释。临床意义和变异分类由 ClinVar 数据库进行。在 SSNS 和 SRNS 患者中，我们发现 0.78% 的致病突变和 3.41% 的可能致病突变。在LAMB2、LMX1B和WT1基因中发现了致病突变，而在 (6/13) LAMB2、 (2/13) LMX1B、 (2/13) TRPC6、 (2/13) PTPRO和 (1/ 13) PMM2基因。在 SSNS 和 SRNS 患者中，大约 46% 的可能致病突变与LAMB2基因有关。我们还检测了 30 个 VUS（意义不确定的变体），通过不同的预测工具发现 (17/30) 致病和 (13/30) 可能致病。

结论

多基因组用于对印度人群中的异质性疾病（如肾病综合征）进行基因筛查。我们发现了致病性、可能致病性和某些 VUS，它们是导致该疾病发病机制的原因。因此，SSNS 和 SRNS 的突变分析对于避免皮质类固醇的副作用、改变免疫抑制剂的强度和防止疾病的进展是必要的。