Abstract: SA-PO0582
Genotype of ADPKD in Greek Patients
Session Information
- Cystic Kidney Diseases: Clinical Research
November 08, 2025 | 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: Monogenic Kidney Diseases
Authors
- Evangelou, Eirini, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece
- Konsta, Maria, Department of Rheumatology, Sismanoglion General Hospital, Athens, Greece
- Poulli, Tsielestina, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece
- Varveri, Maria, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece
- Palaiologou, Danai, Genesis Genoma Lab, Genetics Diagnosis, Clinical Genetics & Research, Athens, Greece
- Poula, Aggeliki, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece
- Markou, Niki, Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece
- Frangou, Eleni A., Aretaieio Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece
- Tsirpanlis, George I., Department of Nephrology, General Hospital of Athens “G. Gennimatas”, Athens, Greece
Background
Genetic testing in patients with ADPKD provide critical information about the disease and its prognosis. This study aims to investigate the genetic etiology of ADPKD in a cohort of Greek patients.
Methods
A total of 135 ADPKD patients (62 females, median age 24 years, IQR: 17–34) were included in this study. Magnetic Resonance Imaging was performed in 104 patients. Children displayed at least 2-4 cysts in echography. All patients underwent genetic testing, including targeted next-generation sequencing, Sanger sequencing, and Multiplex Ligation-Dependent Probe Amplification.
Results
Genetic analysis confirmed a diagnosis in 126 of 135 patients (93.3%). Variants in the PKD1 gene were detected in 90 patients (66.6%) and 66 (75.9%) of them were truncated. Variants in the PKD2 gene were identified in 20 patients. Genetic variants in genes other than PKD1 and PKD2 were identified in 12 patients (8.9%), including GANAB (3 cases), IFT140 (2 cases), and SEC61B gene (2 cases), the later, a father and his son, classified as variant of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) guidelines. In two other cases involving a father 73 and a daughter 35 years old, two variants were identified in PKHD1 and COL4A3 genes, both classified as VUS. Finally, three cases with multiple kidney cysts showed variants in DNAJB11, SEC63, and SLC3A1 genes. Simultaneous variants in PKD1 and other genes were observed in 4 patients. In 3 related patients, in PKD1 and PKHD1 genes, both classified as VUS. In another case, a pathogenic frameshift mutation in PKD1 and a pathogenic missense mutation in COL4A4 were detected. Overall, 42.9% of identified variants were classified as pathogenic, 50% as likely pathogenic, and 7.1% (9 cases) as VUS.
Conclusion
This study highlights the genetic diversity of ADPKD in Greek patients. The predominance of the variants identified in PKD1 and PKD2 genes, particularly those leading to truncated Polycystin-1 production, underscores their critical role in ADPKD. The identification of variants in other genes such as GANAB, IFT14O etc reveals the genetic heterogeneity of the disease. The findings also reveal the complexity of genetic counselling, as double mutations and VUS are frequently observed.