Abstract: FR-PO612
A Case of Early Onset Autosomal Dominant Polycystic Kidney Disease Caused by GANAB Mutation
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1001 Genetic Diseases of the Kidney: Cystic
Authors
- Waldrop, Elizabeth, Texas Tech University Health Sciences Center, Amarillo, Texas, United States
- Al-Obaide, Mohammed A., Texas Tech University Health Sciences Center, Amarillo, Texas, United States
- Vasylyeva, Tetyana L., Texas Tech University Health Sciences Center, Amarillo, Texas, United States
Introduction
Autosomal Dominant Polycystic Kidney Disease (ADPKD) typically results from mutations in the PKD1 and PKD2 genes, which code for polycystin 1 and polycystin 2 respectively. Mutations in these genes promote renal cystic dysplasia and are a significant cause of End-Stage Kidney Disease (ESKD). PKD3 is related to GANAB gene mutation and represents mid- and late adulthood. We report a description of a case of ADPKD in a 12-year-old female with dual mutations in PKD1 and GANAB genes and presented bilateral renal cysts in adolescence.
Case Description
A 12-year-old female presented to the local emergency room with persistent intense left flank pain. Dipstick showed large blood and abdominal CT showed 4 mm obstructing calculus in proximal left ureter, nephrolithiasis with minimal scaring in upper pole of left kidney, multiple bilateral renal cysts with the dominant on the left kidney at 2.8 mm. Non-calcified 2 mm right lower lobe pulmonary nodules was also identified. Renal function was preserved with BUN of 11 mg/dl and creatinine of 0.6 mg/dl, electrolytes were within normal range. The patient was treated with pain control medications and hydration with improvement and was referred to a nephrologist. Renal ultrasound (RUS) showed multiple bilateral cysts. The right kidney measured 10.5 cm x 4.9 cm x 4.8 cm and the left kidney measured 9.8 cm x 4.7 cm x 5.0 cm. Renal cysts were present bilaterally with some displaying thick internal septation. The largest cyst was present in the left kidney, measuring 3.3 mm. Using genomic DNA from the submitted specimens, the exonic regions and flanking splice junctions captured and sequenced by NGS and compared to the human genome build of non-mutated genes of interest. The results returned positive for GANAB, variant p.R61X generated nonsense mutation; and PKD1, variant p.P61L generated missense mutation. The GANAB mutation classified as pathogenic variant and the PKD1 mutation classified as a variant of uncertain significance.
Discussion
The presented case is the first reported pediatric case with dual mutation (PKD1 and GANAB) and nephrolithiasis. The data present unreported novel GANAB mutations to expand the mutation spectrum reported by Porath et al., 2017. Knowledge of spectrum variety in pediatric patients with cystic kidney disease might direct early diagnostic and open prospective for gene therapy.