[PLCE1 mutation-induced end-stage renal disease presenting with massive proteinuria: a family analysis and literature review]

Abstract

Objectives: To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations.

Methods: A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations.

Results: 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 PLCE1 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.

Conclusions: Compound heterozygous mutations in the PLCE1 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.

Keywords: Child; End-stage renal disease; Kidney transplantation; Medullary sponge kidney; PLCE1 gene.

图1. 患儿肾脏病理活检 A为肾活检光镜示FSGS（过碘酸六胺银染色，×40，比例尺=50 μm）；B为肾活检电镜示足突广泛融合（比例尺=2 μm）。红色箭头指示病变部位。

图2. 先证者家系谱 罗马数字表世代，阿拉伯数字表同代个体顺序。

图3. 变异位点对PLCE1蛋白空间结构的影响 A为野生型PLCE1蛋白结构；B为变异型蛋白p.R321X的结构；C为变异型蛋白p.K1085Nfs*8的结构；D为变异型蛋白p.R561Q的结构；E为变异型蛋白p.D554N的结构。湖蓝色代表α螺旋，紫色代表β折叠，粉色线圈代表Loop结构；图中每个颜色代表不同的原子，黄色为C原子，蓝色为N原子，红色为O原子。