Journal Article

Hepatocyte nuclear factor-1β gene deletions—a common cause of renal disease

Emma L. Edghill, Richard A. Oram, Martina Owens, Karen L. Stals, Lorna W. Harries, Andrew T. Hattersley, Sian Ellard and Coralie Bingham

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 2, pages 627-635
Published in print February 2008 | ISSN: 0931-0509
Published online October 2007 | e-ISSN: 1460-2385 | DOI:
Hepatocyte nuclear factor-1β gene deletions—a common cause of renal disease

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Background. Hepatocyte nuclear factor-1β (HNF-1β) is a critical transcription factor in pancreatic and renal development. Our previous report identified HNF-1β mutations in 23/160 patients with unexplained renal disease. The most common phenotype is renal cysts, which is frequently associated with early-onset diabetes in the renal cysts and diabetes (RCAD) syndrome. HNF-1β gene deletions have recently been shown to cause renal malformations and early-onset diabetes.

Methods. We developed a multiplex ligation-dependent probe amplification (MLPA) assay for HNF-1β gene dosage analysis and tested patients with unexplained renal disease in whom mutations had not been found by sequencing.

Results. Whole HNF-1β gene deletions were detected in 15/133 probands. Renal cysts were present in 13/15, including three with glomerulocystic kidney disease and one with cystic renal dysplasia. Renal function ranged from normal to transplantation aged 3 years. Ten probands had diabetes (nine having RCAD). In addition, four had abnormal liver function tests, two showed pancreatic atrophy and 3/10 female probands had uterine malformations. Whole HNF-1β gene deletions are a common cause of developmental renal disease, particularly renal cystic disease with or without diabetes.

Conclusions. The phenotype associated with deletions or coding region/splicing mutations is very similar suggesting that haploinsufficiency is the underlying mechanism. Patients with features suggestive of the HNF-1β clinical phenotype should be tested for mutations both by sequence and dosage analysis.

Keywords: HNF-1β; renal disease; diabetes; deletion mutation

Journal Article.  3991 words.  Illustrated.

Subjects: Nephrology

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