Diagnosing Mendelian Kidney Disease: Hidden Niches in the (Kidney) Genome

Ekici AB, Knaup K, Schaeffer C, Schneider K, Wopperer F, Wiesener A, Dieterle A, Buchholz B, Schiffer M, Saake M, Vasko R, Wons A, Schuhmann S, Vasileiou G, Wiesmann da Silva Reis A, Rampoldi L, Pasutto F, Wiesener M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

American Journal of Kidney Diseases Elsevier

Book Volume: 88

Pages Range: 636-640

Journal Issue: 4

DOI: 10.1053/j.ajkd.2026.05.015

Abstract

A certain proportion of patients with Mendelian diseases are overlooked, although substantial technical advances in molecular genetics have been achieved. Massively parallel sequencing (MPS) increasingly identifies genetic variants of unknown significance, which may remain clinically unhelpful. Furthermore, difficult niches in the genome exist, which cannot be solved by standard MPS. In the reported family, autosomal dominant kidney disease leading to renal failure in middle adulthood runs through the maternal and paternal family. Comprehensive genetic analyses and customized functional evaluation solved the genetic etiologies: autosomal dominant polycystic kidney disease (ADPKD- PKD1 , maternal) and autosomal dominant tubulointerstitial kidney disease (ADTKD- UMOD, paternal), with the index patient suffering from both diseases. The pathogenic variant in PKD1 (c.2180T>C, p.(Leu727Pro)) was not identified by exome sequencing but was unveiled by traditional long-range amplification protocols and whole genome sequencing. The ease of use of MPS increasingly tempts nonspecialized genetic laboratories to perform broad analyses of numerous diseases, which in specific cases may worsen the quality of investigations, ie, for the relatively frequent ADPKD.

Authors with CRIS profile

Arif Bülent Ekici Lehrstuhl für Humangenetik Karl Knaup Department of Medicine 4 – Nephrology and Hypertension Florian Wopperer Department of Medicine 4 – Nephrology and Hypertension Anne Dieterle Department of Medicine 4 – Nephrology and Hypertension Björn Buchholz Department of Medicine 4 – Nephrology and Hypertension Mario Schiffer Lehrstuhl für Innere Medizin IV Marc Saake Institute of Radiology Sarah Eller Institute of Human Genetics Georgia Vasileiou Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Francesca Pasutto Medizinische Fakultät Michael Wiesener Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Ospedale San Raffaele (früher: Centro San Raffaele del Monte Tabor Foundation) IT Italy (IT) B. Braun Gesundheitszentrum Bad Kissingen MVZ GmbH DE Germany (DE) B. Braun Gesundheitszentrum Bad Neustadt MVZ GmbH DE Germany (DE)

How to cite

APA:

Ekici, A.B., Knaup, K., Schaeffer, C., Schneider, K., Wopperer, F., Wiesener, A.,... Wiesener, M. (2026). Diagnosing Mendelian Kidney Disease: Hidden Niches in the (Kidney) Genome. American Journal of Kidney Diseases, 88(4), 636-640. https://doi.org/10.1053/j.ajkd.2026.05.015

MLA:

Ekici, Arif Bülent, et al. "Diagnosing Mendelian Kidney Disease: Hidden Niches in the (Kidney) Genome." American Journal of Kidney Diseases 88.4 (2026): 636-640.

BibTeX: Download