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Kidney Int. 2014 Sep;86(3):589-99. doi: 10.1038/ki.2014.72. Epub 2014 Mar 26.

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

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Institute for Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
1] Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany [2] Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Genetics, Assistance Publique-Hopitaux de Paris, Necker Hospital, Paris, France.
Institute for Human Genetics, University of Cologne, Cologne, Germany.
Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Nephrology and Hypertension, Hospital of Offenburg, Offenburg, Germany.
1] Renal Division, University Hospital Freiburg, Freiburg, Germany [2] BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany.
Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Department of Renal Medicine, St George Clinical School, University of New South Wales, Kogarah, New South Wales, Australia.
Department of Renal Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
KfH Nierenzentrum Miesbach, Miesbach, Germany.
1] Inserm, U983, Necker Hospital, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France.
Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.


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.

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