Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?
Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?
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DOI：
10.1007/s00467-017-3838-6
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Lennon R
中科院分区：
文献类型：
--
作者：
Preston R;Stuart HM;Lennon R
类固醇抵抗性肾病综合征（SRNS）是儿童慢性肾脏疾病的常见原因，具有快速发展为终末期肾脏疾病的显著风险。超过50种SRNS单基因病因的鉴定揭示了足细胞相关蛋白在蛋白尿发病机制中的功能障碍，强调了它们在肾小球功能中的重要作用。高通量测序的最新技术进步使SRNS患者的适应症驱动基因面板检测成为可能。基因检测的可用性，加上单基因SRNS显著的表型变异性，给临床医生指导基因检测带来了独特的挑战。这突出表明需要明确的临床指南，为SRNS的突变筛查提供系统的方法。发现致病突变的可能性与发病年龄呈负相关，阳性家族史或存在肾外表现的可能性增加。一个明确的分子诊断可以允许个性化的治疗方法，断奶免疫抑制治疗，避免肾活检和提供准确的，信息灵通的遗传咨询。新的致病突变的鉴定将继续揭示肾小球疾病的致病机制，并为足细胞生物学和肾小球功能提供新的见解。
Steroid-resistant nephrotic syndrome (SRNS) is a common cause of chronic kidney disease in childhood and has a significant risk of rapid progression to end-stage renal disease. The identification of over 50 monogenic causes of SRNS has revealed dysfunction in podocyte-associated proteins in the pathogenesis of proteinuria, highlighting their essential role in glomerular function. Recent technological advances in high-throughput sequencing have enabled indication-driven genetic panel testing for patients with SRNS. The availability of genetic testing, combined with the significant phenotypic variability of monogenic SRNS, poses unique challenges for clinicians when directing genetic testing. This highlights the need for clear clinical guidelines that provide a systematic approach for mutational screening in SRNS. The likelihood of identifying a causative mutation is inversely related to age at disease onset and is increased with a positive family history or the presence of extra-renal manifestations. An unequivocal molecular diagnosis could allow for a personalised treatment approach with weaning of immunosuppressive therapy, avoidance of renal biopsy and provision of accurate, well-informed genetic counselling. Identification of novel causative mutations will continue to unravel the pathogenic mechanisms of glomerular disease and provide new insights into podocyte biology and glomerular function.
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