Abstract: FR-PO708
Expanding the Variability of the ADPKD-GANAB Clinical Phenotype: A New Family of Italian Ancestry
Session Information
- Cystic Kidney Diseases: Clinical/Translational
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Izzi, Claudia, Spedali Civili di Brescia, Montichiari, Brescia, Italy
- Delbarba, Elisa, University of Brescia, Montichiari (Brescia), Italy
- Econimo, Laura, Spedali Civili di Brescia, Montichiari, Brescia, Italy
- Gnutti, Barbara, Spedali Civili di Brescia, Brescia, Italy
- Mazza, Cinzia, Spedali Civili di Brescia, Brescia, Italy
- Scolari, Francesco, University of Brescia, Montichiari (Brescia), Italy
Introduction
Causative GANAB mutations have been described reported in only 12 families, 9 diagnosed with late-onset mild ADPKD and 3 with ADPLD. We describe a new family with mild, late-onset ADPKD due to p. R839W GANAB mutation, previously reported in an ADPLD patient requiring liver transplantation.
Case Description
Diagnosis of ADPKD was made in a 45-year old man during pre-surgical screening for umbilical and inguinal hernia repair. Hematuria, hypertension and aortic root dilatation were documented. At age 52, he experienced acute flank pain. Abdomen CT scan showed bilateral renal cysts (TKV 565 cc), nephrolithiasis, normal-sized liver with multiple cysts, and colonic diverticuli; renal function was normal. PKD1-PKD2 NGS and MLPA analyses were negative; analysis of additional PKD related genes showed a heterozygous p. R839W GANAB mutation. Familial study revealed p. R839W GANAB mutation in the mother. The elderly parents had normal renal function, normal-sized kidneys with multiple bilateral kidney cysts (mainly parapelvic in the father). The ADPKD-GANAB affected mother had no liver cysts on CT scan. The father has been studied for PKD related genes and no mutation was found.
Discussion
Since ADPKD-GANAB is a rare condition, we need further families to better characterize the phenotypic features of this new cystic disease. In our family, the p. R839W GANAB mutation, previously associated with severe ADPLD, was associated with a mild ADPKD, although showing several renal and extrarenal manifestations. The overlapping cystic phenotype and the plethora of renal and extrarenal manifestations are in agreement with the hypothesis that in GANAB disease, hepatic and renal cysto-genesis is the result of the common defective polycystin-1 pathway.