Abstract: SA-PO581
Characterizing Kidney and Liver Cysts in Monoallelic PKHD1 Individuals Identified in a Population-Based Study
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
- Elbarougy, Doaa E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Jawaid, Tabinda, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Yang, Hana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- McDonnell, Shannon K., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Frank, Jacob A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ma, Jun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Chebib, Fouad T., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Larson, Nicholas B., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Biallelic-PKHD1 pathogenic variants are associated with ARPKD, while monoallelic-PKHD1 mutations have recurrently been related to mild liver or kidney cysts. Here, we employed the population-based Mayo Clinic Biobank (MCBB) cohort with whole exome sequencing data to clinically characterize monoallelic-PKHD1 individuals.
Methods
A cohort of 52,786 MCBB individuals was screened for known pathogenic variants in PKHD1 and clinical records were screened using Mayo Data Explorer. Kidney and liver cysts were counted via automated segmentation or manually, respectively. Monoallelic-PKHD1 individuals identified from ARPKD families and through genetic screening of cystic subjects in the Mayo PKD Center (MPC) were also characterized and compared to the MCBB PKHD1 carriers.
Results
A total of 975 PKHD1 carriers were identified in MCBB (1.85%); 267 (27.4%) had protein truncating and 708 (72.6%) non-truncating pathogenic variants. Based on radiology reports of the 581 with abdominal imaging, 142 (24.4%) had both kidney and liver cysts, 149 (25.6%) only kidney cysts, and 57 (9.8%) only liver cysts; 30.6% with appropriate imaging had nephrolithiasis. ICD9/10 codes for kidney or liver cysts were positive in 37 (6.5%) patients, including three with ADPKD codes. Figure 1 shows the number of kidney (A) or liver (B) cysts per patient out of 259 MCBB individuals with analyzed imaging; 17% and 15.8% had ≥10 kidney or liver cysts, respectively. Corresponding frequencies were 12.5% and 25% in 16 ARPKD family members and 70.6% and 51.5% in 33 MPC sporadic individuals. With age adjustment, the mean eGFR ±SE was higher in the MCBB group (74.9±0.7), than in the ARPKD families (62.5±5.8; p=0.04) and the MPC sporadic individuals (57.2±5; p<0.001). A total of 25 PKHD1 MCBB cases had CKD5, but in each case other comorbidities were identified.
Conclusion
Carriers of PKHD1 pathogenic variants are common and kidney and/or liver cysts are often seen, but polycystic kidneys and/or livers are quite rare (<20% of individuals), as is eGFR decline.
Funding
- NIDDK Support