Abasi Reyila, Zhu Zhen-Chun, Lin Zhi-Lang, Zhuang Hong-Jie, Jiang Xiao-Yun, Pei Yu-Xin
Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2025 May 15;27(5):580-587. doi: 10.7499/j.issn.1008-8830.2411029.
To summarize the clinical and genetic characteristics of end-stage renal disease caused by gene mutations.
A retrospective analysis of the clinical and genetic features of three children from a family with gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by gene mutations.
The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease. Renal biopsy showed focal segmental glomerulosclerosis. Two years and five months after kidney transplantation, the patient had persistent negative proteinuria and normal renal function. Whole-exome sequencing identified two pathogenic heterozygous variants: c.961C>T and c.3255_3256delinsT, with c.3255_3256delinsT being a novel mutation. Family screening revealed no renal involvement in the parents, but among five siblings, one brother died at age of 4 years from end-stage renal disease. A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney, with proteinuria resolving after one year of follow-up. A 3-year-old brother died after kidney transplantation due to severe pneumonia. The literature review included 45 patients with hereditary kidney disease caused by gene mutations. The main clinical phenotype was nephrotic syndrome (87%, 39/45), and renal pathology predominantly showed focal segmental glomerulosclerosis (57%, 16/28). No mutation hotspots were identified.
Compound heterozygous mutations in the gene can lead to rapid progression of the disease to end-stage renal disease, with favorable outcomes following kidney transplantation. Family screening is crucial for early diagnosis, and medullary sponge kidney may be a novel phenotype associated with these gene mutations.
总结由基因突变引起的终末期肾病的临床和遗传特征。
对一个有基因突变的家族中的三名儿童的临床和遗传特征进行回顾性分析，并对由基因突变引起的遗传性肾病病例进行文献综述。
先证者为一名8岁男性，表现为4期慢性肾病肾病综合征。肾活检显示局灶节段性肾小球硬化。肾移植两年零五个月后，患者蛋白尿持续转阴，肾功能正常。全外显子测序鉴定出两个致病性杂合变异：c.961C>T和c.3255_3256delinsT，其中c.3255_3256delinsT为新突变。家系筛查显示父母无肾脏受累，但在五个兄弟姐妹中，一个兄弟4岁时死于终末期肾病。一名7岁的姐妹出现蛋白尿和双侧髓质海绵肾，随访一年后蛋白尿消失。一名3岁的兄弟肾移植后因严重肺炎死亡。文献综述纳入了45例由基因突变引起的遗传性肾病患者。主要临床表型为肾病综合征（87%，39/45），肾脏病理主要表现为局灶节段性肾小球硬化（57%，16/28）。未发现突变热点。
该基因的复合杂合突变可导致疾病迅速进展至终末期肾病，肾移植后预后良好。家系筛查对早期诊断至关重要, 髓质海绵肾可能是与这些基因突变相关的新表型。
