ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO589

New Mutation Associated with Polycystic Kidney Disease Type I: A Case Report

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Rai, Vanya, Mayo Clinic Research Rochester, Rochester, Minnesota, United States
  • Singh, Manisha, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Holthoff, Joseph H., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent heritable disorders, characterized by the progressive development of kidney cysts leading to renal failure. The disease is primarily caused by mutations in the PKD1 and PKD2 genes, which account for approximately 85% and 15% of cases, respectively. The PKD1 gene, encoding polycystin-1, plays a crucial role in maintaining renal tubular structure and function. This case report describes a previously unreported mutation in the PKD1 gene, identified in a family involving an aunt and her niece, both diagnosed with ADPKD.

Case Description

The index case, a 56-year-old female with chronic kidney disease stage 3b secondary to ADPKD and hypertension, exhibited a strong family history of polycystic kidney disease (PKD). Initial genetic evaluations did not identify any recognized pathogenic mutations, leading to a more detailed genetic investigation, which revealed a novel in-frame deletion in the PKD1 gene, a mutation previously not known to be pathogenic. This mutation was also found in her niece, who presented with severe manifestations of the diease from an early age. The familial consistency of these presentations prompted the investigation into this genetic mutation's potential significance in disease phenotype and progression.

Discussion

The identification of a heterozygous six-nucleotide deletion, c.2084_2089del, resulting in the in-frame deletion of two amino acids, p.Pro695_Ala696del, in the PKD1 gene has significant implications for the clinical outcomes in both patients. The discovery of this novel PKD1 mutation highlights the necessity of considering novel genetic variants in patients with typical clinical presentations but without identifiable mutations in the common loci associated with ADPKD. It also emphasizes the need for continuous updates to genetic data and the benefits of comprehensive genetic screening in families with a history of the disease.