Universität zu Köln

Wopperer, Florian J., Knaup, Karl X., Stanzick, Kira J., Schneider, Karen, Jobst-Schwan, Tilman, Ekici, Arif B., Uebe, Steffen, Wenzel, Andrea, Schliep, Stefan, Schuerfeld, Carsten, Seitz, Randolf, Bernhardt, Wanja, Goedel, Markus, Wiesener, Antje, Popp, Bernt ORCID: 0000-0002-3679-1081, Stark, Klaus J., Groene, Hermann-Josef, Friedrich, Bjoern, Weiss, Martin, Basic-Jukic, Nikolina ORCID: 0000-0002-0221-2758, Schiffer, Mario, Schroeppel, Bernd, Huettel, Bruno, Beck, Bodo B., Sayer, John A., Ziegler, Christine, Buettner-Herold, Maike, Amann, Kerstin, Heid, Iris M., Reis, Andre, Pasutto, Francesca and Wiesener, Michael S. (2022). Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases. Kidney Int., 102 (2). S. 405 - 421. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wopperer, Florian J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knaup, Karl X. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stanzick, Kira J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Jobst-Schwan, Tilman UNSPECIFIED UNSPECIFIED UNSPECIFIED Ekici, Arif B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Uebe, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wenzel, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Schliep, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuerfeld, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Seitz, Randolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernhardt, Wanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Goedel, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesener, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Popp, Bernt UNSPECIFIED orcid.org/0000-0002-3679-1081 UNSPECIFIED Stark, Klaus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Groene, Hermann-Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrich, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Basic-Jukic, Nikolina UNSPECIFIED orcid.org/0000-0002-0221-2758 UNSPECIFIED Schiffer, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeppel, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Huettel, Bruno UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Bodo B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sayer, John A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziegler, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner-Herold, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Amann, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Heid, Iris M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reis, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasutto, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesener, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-694268
DOI:	10.1016/j.kint.2022.04.031
Journal or Publication Title:	Kidney Int.
Volume:	102
Number:	2
Page Range:	S. 405 - 421
Date:	2022
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SEQUENCE VARIANTS; UMOD GENE; MUTATIONS; NEPHROPATHY; MICROHEMATURIA; EXPRESSION; COL4A5; FAMILY; ADTKD Multiple languages Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69426