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Abstract: FR-PO710

Clinical Variability in PKD2-Linked Families with the Same Germ-Line Mutation

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Corradi, Valentina, San Bortolo Hospital, Vicenza, Italy
  • Giuliani, Anna, San Bortolo Hospital, Vicenza, Italy
  • Caprara, Carlotta, IRRIV, Vicenza, Italy
  • Gastaldon, Fiorella, San Bortolo Hospital, Vicenza, Italy
  • de Cal, Massimo, San Bortolo Hospital, Vicenza, Italy
  • Ronco, Claudio, University of Padova, IRRIV, San Bortolo Hospital, Vicenza, Italy

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited renal cystic disease. It is genetically heterogeneous:72-75% of ADPKD cases are related to mutations in the PKD1, 15-18 % to PKD2 and the remaining 7–10% of affected are genetically unresolved (GUR). Both genes are characterized by high level of allelic heterogeneity. It is rare to identify the same germ-line mutation in different families, since mutations are “private”. The age at disease onset, the severity, and the clinical outcome contribute to the intra and interfamilial variability.
Aim of the study was to evaluate the clinical characteristics of PKD2 gene-linked families with the same germ-line mutation.


Patients (pts) with ADPKD were enrolled and followed prospectively. Diagnosis of ADPKD was made upon the revised Ravine’s criteria. Complete clinical details were recorded, including family history and pedigree. We performed Sanger sequencing analysis to identify mutations. The eGFR was calculated CKD-EPI equation. The progression of CKD was determined by the change in eGFR per year. Data were shown as mean ± sd or median (min-max).


Twenty-five pts (14male) were included in the analysis, belonging to 10 PKD2gene-linked families with the same germ-line nonsense mutation (c.2533C>T, p.Arg845Ter). 7/10 families had their origin from the same geographical area. The other three families originated from an area 100 km away.
Four of them reached ESRD (61 ± 9 yrs) belonging to different families. In 3/4 families at least one relative of ESRD pts did not required RRT at the same age. Moreover, in one family 2 relatives are not even CKD.
Nine patients (43 ± 14yrs) are still not affected by CKD; 6/9 pts have at least one ESRD relative. Eleven patients (61 ± 9.6 yrs) have CKD stage 2-3 and a progression rate estimated of 2.3 ml/min/year (0.73-5.1). One of them is a fast progressor and he is in treatment with Tolvaptan.


We found the same PKD2 germline mutation in 10 families maybe due to a founder effect in our region. High intra-interfamilial variability in ADPKD pedigrees was observed, despite the same germline mutation.
This could be explained by other clinical or genetic factors (environmental, SNPs, modifier genes, etc) that may affect disease severity.