Renal fibrosis is the common feature of autosomal dominant tubulointerstitial kidney diseases caused by mutations in mucin 1 or uromodulin

Ekici AB, Hackenbeck T, Moriniere V, Panness A, Büttner M, Uebe S, Janka RM, Wiesener A, Hermann I, Grupp S, Hornberger M, Huber TB, Isbel N, Mangos G, Mcginn S, Soreth-Rieke D, Beck BB, Uder M, Amann KU, Antignac C, Reis A, Eckardt KU, Wiesener MS (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Kidney International Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 86

Pages Range: 589-99

Journal Issue: 3

DOI: 10.1038/ki.2014.72

Abstract

For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently described, MUC1. Affected family members show renal fibrosis in the biopsy and gradually declining renal function, with renal failure usually occurring between the third and sixth decade of life. Here we describe 10 families and define eligibility criteria to consider this type of inherited disease, as well as propose a practicable approach for diagnosis. In contrast to what the frequently used term 'Medullary Cystic Kidney Disease' implies, development of (medullary) cysts is neither an early nor a typical feature, as determined by MRI. In addition to Sanger and gene panel sequencing of the four genes, we established SNaPshot minisequencing for the predescribed cytosine duplication within a distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of 9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On the basis of clinical and pathological characteristics we propose the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' as an improved terminology. This should enhance recognition and correct diagnosis of affected individuals, facilitate genetic counseling, and stimulate research into the underlying pathophysiology.

Authors with CRIS profile

Arif Bülent Ekici Institute of Human Genetics Steffen Uebe Institute of Human Genetics Rolf Matthias Janka Institute of Radiology Michael Uder Lehrstuhl für Diagnostische Radiologie Kerstin Ute Amann Department of Nephropathology André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Kai-Uwe Eckardt Lehrstuhl für Innere Medizin IV

Involved external institutions

Universität zu Köln DE Germany (DE) Assistance Publique-Hôpitaux de Paris (AP-HP) FR France (FR) Royal North Shore Hospital (RNSH) AU Australia (AU) Hôpital Necker-Enfants malades FR France (FR) KfH Kuratorium für Dialyse und Nierentransplantation e.V. DE Germany (DE) University of New South Wales (UNSW) AU Australia (AU) Princess Alexandra Hospital AU Australia (AU) Universitätsklinikum Freiburg DE Germany (DE) Ortenau Klinikum DE Germany (DE)

How to cite

APA:

Ekici, A.B., Hackenbeck, T., Moriniere, V., Panness, A., Büttner, M., Uebe, S.,... Wiesener, M.S. (2014). Renal fibrosis is the common feature of autosomal dominant tubulointerstitial kidney diseases caused by mutations in mucin 1 or uromodulin. Kidney International, 86(3), 589-99. https://dx.doi.org/10.1038/ki.2014.72

MLA:

Ekici, Arif Bülent, et al. "Renal fibrosis is the common feature of autosomal dominant tubulointerstitial kidney diseases caused by mutations in mucin 1 or uromodulin." Kidney International 86.3 (2014): 589-99.

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