ESPN 53rd Annual Meeting

ESPN 2021


 
Congenital nephrotic syndrome: a case report of two sisters with the same mutations but different phenotype
FIORENZA ALFIER 1 SUSANNA NEGRISOLO 2 GERMANA LONGO 3 ANDREA CARRARO 2 DAVIDE MENEGHESSO 3 MATTIA PAROLIN 3 LEONARDO SALVIATI 4 LUISA MURER 2 ELISA BENETTI 3

1- DEPARTMENT OF WOMAN AND CHILDS HEALTH, UNIVERSITY OF PADOVA, PADOVA, ITALY
2- LABORATORY OF IMMUNOPATHOLOGY AND MOLECULAR BIOLOGY OF THE KIDNEY, INSTITUTE OF PEDIATRIC RESEARCH CITTà DELLA SPERANZA, DEPARTMENT OF WOMEN’S AND CHILDREN’S HEALTH, PADUA UNIVERSITY HOSPITAL, PADUA, ITALY
3- PEDIATRIC NEPHROLOGY DIALYSIS AND TRANSPLANT UNIT, DEPARTMENT OF WOMEN’S AND CHILDREN’S HEALTH, PADUA UNIVERSITY HOSPITAL, PADUA, ITALY
4- CLINICAL GENETICS UNIT, DEPARTMENT OF WOMAN AND CHILD HEALTH, UNIVERSITY OF PADOVA, AND IRP CITTà DELLA SPERANZA, PADOVA, ITALY
 
Abstract:

Introduction: Congenital nephrotic syndrome (CNS) is a heterogeneous kidney disorder characterized by early onset of symptoms caused by genetic defects in specific podocyte proteins disrupting the integrity of the filtration barrier. The most common genetic defects involve NPHS1 gene, which encodes nephrin and causes the Finnish type CNS. 

Material and Methods: Herein we report the case of two Chinese sisters with the same mutations but different clinical severity. The younger sister was referred at three months because she developed diffuse oedema associated with massive proteinuria (max 11,6 g/L), hypoalbuminemia (min 14 g/L, range 38-54 g/L), hypothyroidism and hypertension. Renal biopsy showed mesangial hypercellularity and diffuse microcystic dilation of the proximal tubules and ultrastructural analysis showed complete foot process effacement and villous transformation of podocytes with endothelial swelling. On the suspect of CNS, NGS analysis was performed.  The girl was treated with albumin, antithrombin III and immunoglobulin supplements, ACE-inhibitor (ACE-i) and anti-hypertensive drugs. In her family history, parents were healthy and not consanguineous, but her older sister was diagnosed with proteinuria at the age of 2 and was treated with ACE-i in China. At 9 years of age, she had mild proteinuria (1 g/day) and her renal biopsy showed mild mesangial hypercellularity, little microcystic dilation of the proximal tubules and foot process effacement. The genetic test was extended to her. 

Results. NGS analysis highlighted the Fin-minor mutation c.3325C>T (p.Arg1109Ter) and the missense mutation c.928G>A (p.Asp310Asn) in compound heterozygous state in both sisters. 

Conclusions. In CNS is emerging evidence of the possibility of a variable phenotype despite the same genetic variants. Our case highlights profound differences both in clinical presentation and evolution and in histological features between sisters with similar environmental exposure and the same compound heterozygous mutations in NPHS1.