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Kidney Week

Abstract: FR-PO791

First Identification of a Rare PODXL Splice Site Mutation in a Case of Focal Segmental Glomerulosclerosis

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Lin, Fujun, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China

Podocalyxin plays an important role in the regulation of podocyte morphogenesis and function. We recently identified heterozygous PODXL nonsense mutations linked to autosomal dominant focal segmental glomerulosclerosis (FSGS). Here, we reported the first heterozygous PODXL splice site mutation identified in FSGS.

Case Description

A 63-year-old Chinese female was admitted to the ward in December 2018 for persistent proteinuria (maximum 2500mg/24hr) and hypertension (140/90mmHg) for three months. Serum creatinine and albumin were within normal range and renal ultrasound revealed normal sized and echogenic kidneys. Renal biopsy suggested FSGS (Figure 1A-1B). Father of the patient was died of renal failure and no history of renal disease found in other close relatives. Whole exome sequencing performed on the patient revealed a PODXL heterozygous donor splice site variant (c.712+1G>A, rs137907090, allele frequency 0.0002) (Figure 2A), leading to the 585bp deletion including exon 3, the last 337 nucleotides on exon 2 and the first 152 nucleotides on exon 4 (Figure 2B-D). This mutation removed 195 amino acids in-frame in the sialomucin domain. Immunohistochemical showed decreased podocalyxin expression along glomerular capillary (Figure 1C) compared with that of normal control (Figure 1D). Losartan was started and at last follow up in May 2019, 24hr proteinuria was 1500mg and serum creatinine remained within normal range.


This case expands the genetic spectrum of PODXL-associated FSGS and further supported that down-regulation of podocalyxin expression linked to FSGS.

Representative microscopic images of the patient.

Mutation and its consequences.