The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype.

ABSTRACT:

Background

Mutation specific effects in monogenic disorders are rare. We describe atypical Fanconi syndrome caused by a specific heterozygous mutation in HNF4A. Heterozygous HNF4A mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Autosomal dominant idiopathic Fanconi syndrome (a renal proximal tubulopathy) is described but no genetic cause has been defined.

Methods and results

We report six patients heterozygous for the p.R76W HNF4A mutation who have Fanconi syndrome and nephrocalcinosis in addition to neonatal hyperinsulinism and macrosomia. All six displayed a novel phenotype of proximal tubulopathy, characterised by generalised aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypou

SUBMITTER: Hamilton AJ 

PROVIDER: S-EPMC3932761 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature