BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder, leading to end stage renal failure and kidney transplantation in its most serious form. The severity of the disease's manifestation depends on the genetic determination of ADPKD. The huge variability of different phenotypes (even within a single family) is not only modulated by the two main ADPKD genes (PKD1 and PKD2) but also by modifier genes and the whole genetic background. CASE PRESENTATION: This is a report of an ADPKD family with co-inheritance of PKD1 and PKD2 pathogenic variants. The proband, with an extremely serious manifestation of ADPKD (the man was diagnosed in early childhood, and with end stage renal disease aged 23), underwent genetic analysis of PKD1 and PKD2, which revealed the presence of pathogenic mutations in both of these genes. The missense PKD2 mutation p.Arg420Gly came from the proband's father, with a mild ADPKD phenotype. The same mutation of the PKD2 gene and similar mild disease presentation were found in the proband's aunt (father's sister) and her son. The nonsense mutation p.Gln2196* within the PKD1 gene was probably inherited from the proband's mother, who died at the age of 45. It was only discovered post mortem, that the real cause of her death was kidney failure as a consequence of untreated ADPKD. Unfortunately, neither the DNA of the proband's mother nor the DNA of any other family members from this side of the pedigree were available for further examination. The proband underwent successful cadaveric kidney transplantation at the age of 24, and this replacement therapy lasted for the next 15 years. CONCLUSIONS: Here, we present a first case of bilineal ADPKD inheritance in the Czech Republic. This report highlights the significant role of modifier genes in genetic determination of ADPKD, especially in connection with seriously deteriorated disease phenotypes. In our case, the modifying role is probably mediated by the PKD2 gene.

• Keywords
• ADPKD, Bilineal inheritance, Causative mutation, Modifier gene, PKD1/2 gene,
• MeSH
• Adult MeSH
• Genetic Variation genetics   MeSH
• TRPP Cation Channels genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation, Missense genetics   MeSH
• Polycystic Kidney, Autosomal Dominant diagnosis   genetics   MeSH
• Pedigree MeSH
• Aged, 80 and over MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• TRPP Cation Channels MeSH
• polycystic kidney disease 1 protein MeSH Browser
• polycystic kidney disease 2 protein MeSH Browser

Adults with autosomal dominant polycystic kidney disease (ADPKD) and PKD1 mutations have a more severe disease than do patients with PKD2 mutations. The aim of this study was to compare phenotypes between children with mutations in the PKD1/PKD2 genes. Fifty PKD1 children and ten PKD2 children were investigated. Their mean age was similar (8.6 +/- 5.4 years and 8.9 +/- 5.6 years). Renal ultrasound was performed, and office blood pressure (BP), ambulatory BP, creatinine clearance and proteinuria were measured. The PKD1 children had, in comparison with those with PKD2, significantly greater total of renal cysts (13.3 +/- 12.5 vs 3.0 +/- 2.1, P = 0.004), larger kidneys [right/left kidney length 0.89 +/- 1.22 standard deviation score (SDS) vs 0.17 +/- 1.03 SDS, P = 0.045, and 1.19 +/- 1.42 SDS vs 0.12 +/- 1.09 SDS, P = 0.014, successively] and higher ambulatory day-time and night-time systolic BP (day-time/night-time BP index 0.93 +/- 0.10 vs 0.86 +/- 0.05, P = 0.021 and 0.94 +/- 0.07 vs 0.89 +/- 0.04, P = 0.037, successively). There were no significant differences in office BP, creatinine clearance or proteinuria. Prenatal renal cysts (14%), hypertension defined by ambulatory BP (27%) and enlarged kidneys (32%) were observed only in the PKD1 children. This is the first study on genotype-phenotype correlation in children with ADPKD. PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1.

• MeSH
• Blood Pressure Monitoring, Ambulatory MeSH
• Child MeSH
• Phenotype MeSH
• Genotype MeSH
• Hypertension genetics   pathology   physiopathology   MeSH
• TRPP Cation Channels blood   genetics   MeSH
• Blood Pressure genetics   physiology   MeSH
• Kidney diagnostic imaging   MeSH
• Humans MeSH
• Polycystic Kidney, Autosomal Dominant genetics   pathology   physiopathology   MeSH
• Retrospective Studies MeSH
• Ultrasonography MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• TRPP Cation Channels MeSH
• polycystic kidney disease 1 protein MeSH Browser
• polycystic kidney disease 2 protein MeSH Browser