Abstract: SA-PO589
New Mutation Associated with Polycystic Kidney Disease Type I: A Case Report
Session Information
- Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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.