Kidney Week

Abstract: PUB290

Variable Clinical Presentation of DNAJB11-Related Kidney Disease in a Large Family Cluster

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Yandian, Federico, Médica Uruguaya, Montevideo, Montevideo, Uruguay

Federico Yandian, MD

• Facal, Lucia, Médica Uruguaya, Montevideo, Montevideo, Uruguay

Lucia Facal, MD

• Spangenberg, Lucia, Institut Pasteur, Montevideo, Montevideo, Montevideo, Uruguay

Lucia Spangenberg, PhD

• Raggio, Víctor E., Departamento de Genetica, Facultad de Medicina UDELAR, Montevideo, Montevideo, Uruguay

Víctor E. Raggio, MD

• Parnizari, Paula, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Montevideo, Uruguay

Paula Parnizari, MD

• Boggia, Jose, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Montevideo, Uruguay

Jose Boggia, MD, MMSc, PhD

• Noboa, Oscar A., Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Montevideo, Uruguay

Oscar A. Noboa, MD

Introduction

We report a case of DNAJB11-kidney diseaseand its phenotype variability within the family.

Case Description

A 28-year-old woman with histopathologic diagnosis of chronic tubular interstitial nephritis presented to our clinic with a history of kidney insufficiency that progressed to ESRD in the following 3 years. She did not show microhematuria or proteinuria. CT scan without evidence of kidney or hepatic cysts at the time of kidney biopsy.
She had a family history of renal disease. Her mother developed kidney failure requiring initiation of RRT at 45 years. Several of her mother's cousins developed kidney failure. The patient’s cousin, a 35-year-old female with renal cysts but with preserved kidney function and normal urinalysis has a diagnosis of Autosomal Dominant Polycystic Kidney Disease (ADPKD) and has a 4 year-old daughter with renal cysts. Another cousin, a 40-year-old male has a diagnosis of ADPKD that developed kidney failure at 40 years. His deceased father, paternal grandma and paternal uncle developed kidney failure and also had a diagnosis of ADPKD with hepatic involvement.
A presumptive diagnosis of Autosomal Dominant Tubulointerstitial Kidney Disease was made in the index case. Exome sequencing (100x, 100 paired/end) revealed a non-coding novel DNAJB11 mutation (chr3:186295418, -/T, hg19) in the index case and her two cousins.

Discussion

Renal disease associated with DNAJB11 mutations is an emerging field in nephrology that requires attention due to its clinical impact. This genetic entity has a variety of presentations, including renal cystic disease and tubulointerstitial nephropathy. Renal cystic disease related to DNAJB11 manifests with the formation of multiple kidney cysts, which can result in progressive renal dysfunction and eventual kidney failure. These cysts can be simple or complex and are often associated with arterial hypertension and hematuria. On the other hand, tubulointerstitial nephropathy associated with DNAJB11 is characterized by inflammation and fibrosis of the renal tissue, leading to tubular dysfunction and loss of renal function. In summary, DNAJB11-kidney diseaseencompasses a wide range of clinical presentations, from renal cyst formation to tubulointerstitial nephropathy, underscoring the importance of its early recognition and proper management in clinical practice.