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

K. Burgmaier, L. Brinker, F. Erger, BB. Beck, MR. Benz, C. Bergmann, O. Boyer, L. Collard, C. Dafinger, M. Fila, C. Kowalewska, B. Lange-Sperandio, L. Massella, A. Mastrangelo, D. Mekahli, M. Miklaszewska, N. Ortiz-Bruechle, L. Patzer, L....

. 2021 ; 100 (3) : 650-659. [pub] 20210430

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, pozorovací studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21025040

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.

Center for Molecular Medicine Cologne University of Cologne Faculty of Medicine University Hospital Cologne Cologne Germany

Center for Rare Diseases University Hospital Cologne and Medical Faculty University of Cologne Cologne Germany

Centro Materno Infantil do Norte Centro Hospitalar do Porto Porto Portugal

Department of Inherited and Acquired Kidney Diseases Research Clinical Institute for Pediatrics n a acad Y E Veltishev Pirogov Russian National Research Medical University Moscow Russia

Department of Nephrology Kidney Transplantation and Hypertension The Children's Memorial Health Institute Warsaw Poland

Department of Pediatric Gastroenterology Nephrology and Metabolic Diseases Charité Universitätsmedizin Berlin Berlin Germany

Department of Pediatric Nephrology and Hypertension Faculty of Medicine Jagiellonian University Medical College Krakow Poland

Department of Pediatric Nephrology and Kidney Transplantation Necker Hospital APHP Paris University Paris France

Department of Pediatric Nephrology Cerrahpaşa School of Medicine Istanbul University Cerrahpasa Istanbul Turkey

Department of Pediatric Nephrology Medical University of Lublin Lublin Poland

Department of Pediatric Nephrology University Hospitals Leuven Leuven Belgium

Department of Pediatrics Children's Hospital St Elisabeth and St Barbara Halle Germany

Department of Pediatrics Dr von Hauner Children's Hospital University Hospital LMU Munich Germany

Department of Pediatrics Faculty of Medical Sciences in Zabrze Medical University of Silesia Katowice Poland

Department of Pediatrics Université Catholique de Louvain Medical School Saint Luc Academic Hospital Brussels Belgium

Department of Pediatrics University Hospital Cologne and University of Cologne Faculty of Medicine Cologne Germany

Department of Pediatrics University Hospital Motol 2nd Faculty of Medicine Charles University Prague Prague Czech Republic

Division of Nephrology Department of Pediatric Subspecialties Bambino Gesù Children's Hospital IRCCS Rome Italy

Division of Pediatric Nephrology Center for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany

Institute of Human Genetics RWTH University Hospital Aachen Aachen Germany

Institute of Human Genetics University Hospital Cologne and University of Cologne Faculty of Medicine Cologne Germany

KfH Center of Pediatric Nephrology Children's Hospital Munich Schwabing Munich Germany

Medizinische Genetik Mainz Limbach Genetics Mainz Germany

Pediatric Nephrology Dachau Dachau Germany

Pediatric Nephrology Dialysis and Transplant Unit Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milan Italy

Pediatric Nephrology Unit CHU Arnaud de Villeneuve Université de Montpellier Montpellier France

Pediatric Nephrology Unit Hôpital Femme Mère Enfant Hospices Civils de Lyon Centre de référence maladies rénales rares Bron France

PKD Research Group Department of Development and Regeneration KU Leuven Leuven Belgium

Reference centre pediatric nephrology Clinique de l'Espérance Montegnee Belgium

Renal Division Department of Medicine University Freiburg Medical Center Freiburg Germany

University Children's Hospital University Medical Center Hamburg Eppendorf Hamburg Germany

Citace poskytuje Crossref.org

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$a Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants / $c K. Burgmaier, L. Brinker, F. Erger, BB. Beck, MR. Benz, C. Bergmann, O. Boyer, L. Collard, C. Dafinger, M. Fila, C. Kowalewska, B. Lange-Sperandio, L. Massella, A. Mastrangelo, D. Mekahli, M. Miklaszewska, N. Ortiz-Bruechle, L. Patzer, L. Prikhodina, B. Ranchin, N. Ranguelov, R. Schild, T. Seeman, L. Sever, P. Sikora, M. Szczepanska, A. Teixeira, J. Thumfart, B. Uetz, LT. Weber, E. Wühl, K. Zerres, ESCAPE Study group, GPN study group, J. Dötsch, F. Schaefer, MC. Liebau, ARegPKD consortium
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