Burgmaier, Kathrin, Brinker, Leonie, Erger, Florian, Beck, Bodo B., Benz, Marcus R., Bergmann, Carsten, Boyer, Olivia, Collard, Laure, Dafinger, Claudia, Fila, Marc, Kowalewska, Claudia, Lange-Sperandio, Baerbel, Massella, Laura, Mastrangelo, Antonio, Mekahli, Djalila, Miklaszewska, Monika, Ortiz-Bruechle, Nadina, Patzer, Ludwig, Prikhodina, Larisa, Ranchin, Bruno, Ranguelov, Nadejda, Schild, Raphael, Seeman, Tomas, Sever, Lale, Sikora, Przemyslaw ORCID: 0000-0002-5698-6863, Szczepanska, Maria ORCID: 0000-0002-6772-1983, Teixeira, Ana, Thumfart, Julia, Uetz, Barbara, Weber, Lutz Thorsten, Wuehl, Elke, Zerres, Klaus, Doetsch, Joerg, Schaefer, Franz and Liebau, Max Christoph ORCID: 0000-0003-0494-9080 (2021). Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. Kidney Int., 100 (3). S. 650 - 660. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is a severe disease of early childhood that is clinically characterized by fibrocystic changes of the kidneys and the liver. The main cause of ARPKD are variants in the PKHD1 gene encoding the large transmembrane protein fibrocystin. The mechanisms underlying the observed clinical heterogeneity in ARPKD remain incompletely understood, partly due to the fact that genotype-phenotype correlations have been limited to the association of biallelic null variants in PKHD1 with the most severe phenotypes. In this observational study we analyzed a deep clinical dataset of 304 patients with ARPKD from two independent cohorts and identified novel genotype-phenotype correlations during childhood and adolescence. Biallelic null variants frequently show severe courses. Additionally, our data suggest that the affected region in PKHD1 is important in determining the phenotype. Patients with two missense variants affecting amino acids 709-1837 of fibrocystin or a missense variant in this region and a null variant less frequently developed chronic kidney failure, and patients with missense variants affecting amino acids 1838-2624 showed better hepatic outcome. Variants affecting amino acids 2625-4074 of fibrocystin were associated with poorer hepatic outcome. Thus, our data expand the understanding of genotype-phenotype correlations in pediatric ARPKD patients and can lay the foundation for more precise and personalized counselling and treatment approaches.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Burgmaier, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinker, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erger, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Bodo B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benz, Marcus R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergmann, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boyer, OliviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collard, LaureUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dafinger, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fila, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kowalewska, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lange-Sperandio, BaerbelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Massella, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mastrangelo, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mekahli, DjalilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miklaszewska, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz-Bruechle, NadinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patzer, LudwigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prikhodina, LarisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ranchin, BrunoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ranguelov, NadejdaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schild, RaphaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seeman, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sever, LaleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikora, PrzemyslawUNSPECIFIEDorcid.org/0000-0002-5698-6863UNSPECIFIED
Szczepanska, MariaUNSPECIFIEDorcid.org/0000-0002-6772-1983UNSPECIFIED
Teixeira, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thumfart, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uetz, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Lutz ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wuehl, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zerres, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doetsch, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, FranzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liebau, Max ChristophUNSPECIFIEDorcid.org/0000-0003-0494-9080UNSPECIFIED
URN: urn:nbn:de:hbz:38-607166
DOI: 10.1016/j.kint.2021.04.019
Journal or Publication Title: Kidney Int.
Volume: 100
Number: 3
Page Range: S. 650 - 660
Date: 2021
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATIONS; ENCODES; ULTRASOUND; PROTEINMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60716

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