Bilineal inheritance of pathogenic PKD1 and PKD2 variants in a Czech family with autosomal dominant polycystic kidney disease - a case report

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10377114" target="_blank" >RIV/00216208:11110/18:10377114 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/18:10377114

Výsledek na webu

<a href="https://doi.org/10.1186/s12882-018-0978-2" target="_blank" >https://doi.org/10.1186/s12882-018-0978-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12882-018-0978-2" target="_blank" >10.1186/s12882-018-0978-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Bilineal inheritance of pathogenic PKD1 and PKD2 variants in a Czech family with autosomal dominant polycystic kidney disease - a case report

Popis výsledku v původním jazyce

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&apos;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&apos;s father, with a mild ADPKD phenotype. The same mutation of the PKD2 gene and similar mild disease presentation were found in the proband&apos;s aunt (father&apos;s sister) and her son. The nonsense mutation p.G1n2196* within the PKD1 gene was probably inherited from the proband&apos;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&apos;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.

Název v anglickém jazyce

Bilineal inheritance of pathogenic PKD1 and PKD2 variants in a Czech family with autosomal dominant polycystic kidney disease - a case report

Popis výsledku anglicky

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&apos;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&apos;s father, with a mild ADPKD phenotype. The same mutation of the PKD2 gene and similar mild disease presentation were found in the proband&apos;s aunt (father&apos;s sister) and her son. The nonsense mutation p.G1n2196* within the PKD1 gene was probably inherited from the proband&apos;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&apos;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BMC Nephrology

ISSN

1471-2369

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

—

Kód UT WoS článku

000437360400004

EID výsledku v databázi Scopus

2-s2.0-85049525402