Wopperer, Florian J. and Knaup, Karl X. and Stanzick, Kira J. and Schneider, Karen and Jobst-Schwan, Tilman and Ekici, Arif B. and Uebe, Steffen and Wenzel, Andrea and Schliep, Stefan and Schuerfeld, Carsten and Seitz, Randolf and Bernhardt, Wanja and Goedel, Markus and Wiesener, Antje and Popp, Bernt and Stark, Klaus J. and Groene, Hermann-Josef and Friedrich, Bjoern and Weiss, Martin and Basic-Jukic, Nikolina and Schiffer, Mario and Schroeppel, Bernd and Huettel, Bruno and Beck, Bodo B. and Sayer, John A. and Ziegler, Christine and Buettner-Herold, Maike and Amann, Kerstin and Heid, Iris M. and Reis, Andre and Pasutto, Francesca and Wiesener, Michael S. (2022) Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases. KIDNEY INTERNATIONAL, 102 (2). pp. 405-420. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | SEQUENCE VARIANTS; UMOD GENE; MUTATIONS; NEPHROPATHY; MICROHEMATURIA; EXPRESSION; COL4A5; FAMILY; ADTKD; ADTKD; Alport syndrome; exome; MITKD; MUC1; UMOD |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 13:32 |
| Last Modified: | 26 Jan 2024 13:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58356 |
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