Cheong Hae Il
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea.
Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kidney Res Clin Pract. 2020 Mar 31;39(1):7-16. doi: 10.23876/j.krcp.20.001.
Steroid-resistant nephrotic syndrome (SRNS) is a common cause of chronic kidney disease in children, and a considerable number of patients progress to end-stage renal disease. SRNS is a highly heterogeneous disorder, both clinically and genetically, and more than 50 monogenic causes of SRNS, including isolated and syndromic forms, have been identified. Recent large-cohort studies indicate that at least 30% of childhood-onset SRNS cases are genetic. The benefits of definitive molecular diagnosis by genetic testing include the avoidance of unnecessary and potentially harmful diagnostic procedures (e.g., kidney biopsy) and treatment (e.g., steroid and immunosuppressants), detection of rare and potentially treatable mutations (e.g., coenzyme Q10 biosynthesis pathway defect), prediction of prognosis (e.g., posttransplant recurrence), and providing precise genetic counseling. Furthermore, the identification of novel disease-causing genes could provide new insights into the pathogenic mechanisms of SRNS. Therefore, whenever accessible and affordable, genetic testing is recommended for all pediatric patients with SRNS, and should certainly be performed in patients with a higher probability of genetic predisposition based on genotype-phenotype correlation data. The genetic testing approach should be determined for each patient, and clinicians should, therefore, be aware of the advantages and disadvantages of methods currently available, which include Sanger sequencing, gene panel testing, and whole-exome or whole-genome sequencing. Importantly, the need for precise and thorough phenotyping by clinicians, even in the era of genomics, cannot be overemphasized. This review provides an update on recent advances in genetic studies, a suggested approach for the genetic testing of pediatric patients with SRNS.
类固醇抵抗性肾病综合征（SRNS）是儿童慢性肾脏病的常见病因，相当一部分患者会进展至终末期肾病。SRNS在临床和遗传方面都是一种高度异质性疾病，已确定了50多种导致SRNS的单基因病因，包括孤立型和综合征型。最近的大型队列研究表明，至少30%的儿童期发病的SRNS病例是遗传性的。通过基因检测进行明确分子诊断的益处包括避免不必要的和潜在有害的诊断程序（如肾活检）和治疗（如类固醇和免疫抑制剂），检测罕见的和可能可治疗的突变（如辅酶Q10生物合成途径缺陷），预测预后（如移植后复发），以及提供精确的遗传咨询。此外，鉴定新的致病基因可为SRNS的致病机制提供新的见解。因此，只要可行且负担得起，建议对所有患有SRNS的儿科患者进行基因检测，对于根据基因型-表型相关性数据具有较高遗传易感性概率的患者，当然应该进行检测。应针对每位患者确定基因检测方法，因此临床医生应了解目前可用方法的优缺点，这些方法包括桑格测序、基因panel检测以及全外显子组或全基因组测序。重要的是，即使在基因组学时代，临床医生进行精确和全面表型分析的必要性也再怎么强调都不为过。本综述提供了遗传研究的最新进展，以及对患有SRNS的儿科患者进行基因检测的建议方法。
