类固醇耐药性肾病综合征(SRNS)是儿童终末期肾病的第二大常见原因,主要与局灶节段性肾小球硬化(FSGS)相关。基因组科学的进展使得能够在20-30%的SRNS患者中鉴定致病变异。
■我们使用全外显子组测序来探索儿童SRNS的遗传原因。完全正确,回顾性纳入我院2018年至2022年的101例SRNS患者和13例肾病性蛋白尿和FSGS患者。对于已知的单基因原因分析,通过查阅OMIM数据库和文献,我们生成了71个已知的SRNS基因列表。
■在我们的23.68%的队列中发现了导致变异,我们队列中最常见的突变基因是WT1(7/27),NPHS1(3/27),ADCK4(3/27),ANLN(2/27)五名患者携带表型基因变异,包括MYH9,MAFB,TTC21B,AGRN,FAT4在先天性肾病综合征和综合征SRNS的两个亚型组中,变异检出率最高。总的来说,我们鉴定的68.75%的变体是新的,并且以前在文献中没有报道过。
■全面的遗传分析是实现基因诊断的临床益处的关键。我们建议所有患有SRNS的儿童都接受基因检测,尤其是那些早发性和肾外表型。
UNASSIGNED: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20-30% of SRNS patients.
UNASSIGNED: We used whole exome sequencing to explore the genetic causes of SRNS in children. Totally, 101 patients with SRNS and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature.
UNASSIGNED: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel and have not been previously reported in the literature.
UNASSIGNED: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early-onset and extrarenal phenotypes.