Variable phenotype in HNF1B mutations: Extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract

Leire Madariaga, Alejandro García-Castaño, Gema Ariceta, Rosa Martínez-Salazar, Aníbal Aguayo, Luis Castaño

Research output: Contribution to journalArticleResearch

8 Citations (Scopus)

Abstract

© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. Background. Mutations in hepatocyte nuclear factor 1B (HNF1B) have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Diabetes and other less frequent anomalies have also been described. Variable penetrance and intrafamilial variability have been demonstrated including severe prenatal phenotypes. Thus, it is important to differentiate this entity from others with similar clinical features and perform confirmatory molecular diagnosis. Methods. This study reports the results of HNF1B screening in a cohort of 60 patients from 58 unrelated families presenting with renal structural anomalies and/or non-immune glucose metabolismalterations, and other minor features suggesting HNF1B mutations. Results. This study identified a pathogenic variant in 23 patients from 21 families. The most frequent finding was bilateral cystic dysplasia or hyperechogenic kidneys (87% of patients). Sixty percent of them also fulfilled the criteria for impaired glucose metabolism, and these were significantly older than those patients with an HNF1B mutation but without diabetes or prediabetes (14.4 versus 3.3 years, P<0.05). Furthermore, patients with HNF1B mutations had higher frequency of pancreatic structural anomalies and hypomagnesaemia than patients without mutations (P<0.001 and P = 0.003, respectively). Hyperuricaemia and increased liver enzymes were detected in some patients as well. Conclusions. Renal anomalies found in patients with HNF1B mutations are frequently unspecific and may resemble those found in other renal pathologies (CAKUT, ciliopathies). Active searching for extrarenal minor features, especially pancreatic structural anomalies or hypomagnesaemia, could support the indication for molecular diagnosis to identify HNF1B mutations.
Original languageEnglish
Pages (from-to)373-379
JournalCKJ: Clinical Kidney Journal
Volume12
DOIs
Publication statusPublished - 1 Jun 2019

Keywords

  • CAKUT
  • HNF1B
  • Hypomagnesaemia
  • MODY
  • Pancreatic structural anomalies

Fingerprint

Dive into the research topics of 'Variable phenotype in HNF1B mutations: Extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract'. Together they form a unique fingerprint.

Cite this