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Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants

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Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. / Burgmaier, Kathrin; Brinker, Leonie; Erger, Florian; Beck, Bodo; Benz, Marcus; Bergmann, Carsten; Boyer, Olivia; Collard, Laure; Dafinger, Claudia; Fila, Marc; Kowalewska, Claudia; Lange-Sperandio, Bärbel; 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; Szczepanska, Maria; Teixeira, Ana; Thumfart, Julia; Uetz, Barbara; Weber, Lutz Thorsten; Wühl, Elke; Zerres, Klaus; ESCAPE Study Group; Dötsch, Jörg; Schaefer, Franz; Liebau, Max Christoph.

in: KIDNEY INT, Jahrgang 100, Nr. 3, 09.2021, S. 650-659.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Burgmaier, K, Brinker, L, Erger, F, Beck, B, Benz, M, Bergmann, C, Boyer, O, Collard, L, Dafinger, C, Fila, M, Kowalewska, C, Lange-Sperandio, B, Massella, L, Mastrangelo, A, Mekahli, D, Miklaszewska, M, Ortiz-Bruechle, N, Patzer, L, Prikhodina, L, Ranchin, B, Ranguelov, N, Schild, R, Seeman, T, Sever, L, Sikora, P, Szczepanska, M, Teixeira, A, Thumfart, J, Uetz, B, Weber, LT, Wühl, E, Zerres, K, ESCAPE Study Group, Dötsch, J, Schaefer, F & Liebau, MC 2021, 'Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants', KIDNEY INT, Jg. 100, Nr. 3, S. 650-659. https://doi.org/10.1016/j.kint.2021.04.019

APA

Burgmaier, K., Brinker, L., Erger, F., Beck, B., Benz, M., Bergmann, C., Boyer, O., Collard, L., Dafinger, C., Fila, M., Kowalewska, C., Lange-Sperandio, B., Massella, L., Mastrangelo, A., Mekahli, D., Miklaszewska, M., Ortiz-Bruechle, N., Patzer, L., Prikhodina, L., ... Liebau, M. C. (2021). Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. KIDNEY INT, 100(3), 650-659. https://doi.org/10.1016/j.kint.2021.04.019

Vancouver

Burgmaier K, Brinker L, Erger F, Beck B, Benz M, Bergmann C et al. Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. KIDNEY INT. 2021 Sep;100(3):650-659. https://doi.org/10.1016/j.kint.2021.04.019

Bibtex

@article{05fab34e27464eada56962e3841b2754,
title = "Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants",
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.",
author = "Kathrin Burgmaier and Leonie Brinker and Florian Erger and Bodo Beck and Marcus Benz and Carsten Bergmann and Olivia Boyer and Laure Collard and Claudia Dafinger and Marc Fila and Claudia Kowalewska and B{\"a}rbel Lange-Sperandio and Laura Massella and Antonio Mastrangelo and Djalila Mekahli and Monika Miklaszewska and Nadina Ortiz-Bruechle and Ludwig Patzer and Larisa Prikhodina and Bruno Ranchin and Nadejda Ranguelov and Raphael Schild and Tomas Seeman and Lale Sever and Przemyslaw Sikora and Maria Szczepanska and Ana Teixeira and Julia Thumfart and Barbara Uetz and Weber, {Lutz Thorsten} and Elke W{\"u}hl and Klaus Zerres and {ESCAPE Study Group} and J{\"o}rg D{\"o}tsch and Franz Schaefer and Liebau, {Max Christoph}",
note = "Copyright {\textcopyright} 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.",
year = "2021",
month = sep,
doi = "10.1016/j.kint.2021.04.019",
language = "English",
volume = "100",
pages = "650--659",
journal = "KIDNEY INT",
issn = "0085-2538",
publisher = "NATURE PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants

AU - Burgmaier, Kathrin

AU - Brinker, Leonie

AU - Erger, Florian

AU - Beck, Bodo

AU - Benz, Marcus

AU - Bergmann, Carsten

AU - Boyer, Olivia

AU - Collard, Laure

AU - Dafinger, Claudia

AU - Fila, Marc

AU - Kowalewska, Claudia

AU - Lange-Sperandio, Bärbel

AU - Massella, Laura

AU - Mastrangelo, Antonio

AU - Mekahli, Djalila

AU - Miklaszewska, Monika

AU - Ortiz-Bruechle, Nadina

AU - Patzer, Ludwig

AU - Prikhodina, Larisa

AU - Ranchin, Bruno

AU - Ranguelov, Nadejda

AU - Schild, Raphael

AU - Seeman, Tomas

AU - Sever, Lale

AU - Sikora, Przemyslaw

AU - Szczepanska, Maria

AU - Teixeira, Ana

AU - Thumfart, Julia

AU - Uetz, Barbara

AU - Weber, Lutz Thorsten

AU - Wühl, Elke

AU - Zerres, Klaus

AU - ESCAPE Study Group

AU - Dötsch, Jörg

AU - Schaefer, Franz

AU - Liebau, Max Christoph

N1 - Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

U2 - 10.1016/j.kint.2021.04.019

DO - 10.1016/j.kint.2021.04.019

M3 - SCORING: Journal article

C2 - 33940108

VL - 100

SP - 650

EP - 659

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 3

ER -