ArticleJournal of medical genetics2014
The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype.
Article in Journal of medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 101 citations in OpenAlex.
- Hypomagnesemia in Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia Syndrome Caused by Pathogenic Variants ofKidney international reports · 2026Article
- Phenotypic Spectrum of HNF4α-Associated Fanconi Renotubular Syndrome.Kidney international reports · 2026Article
- Genetic Screening of Patients With Inherited Fanconi Syndrome.Kidney international reports · 2026Article
- Maturity Onset Diabetes of the Young (MODY): French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins).Orphanet journal of rare diseases · 2026Review
- Renal proteomic landscape of a patient with Fanconi renotubular syndrome carrying a novel GATM variant.Frontiers in physiology · 2026Article
- Genetic and Clinical Characterization of a Large Cohort with Suspected Monogenic Stone Disease.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- Presence of mitochondrial dysfunction in a case of Fanconi syndrome with normoglycemic MODY1.CEN case reports · 2025Article
- Genetic background of neonatal hypokalemia.Pediatric nephrology (Berlin, Germany) · 2025Review
- Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.Nature genetics · 2024Article
- Functional characterization of HNF4A gene variants identify promoter and cell line specific transactivation effects.Human molecular genetics · 2024Article
- De novo HNF4A-associated atypical Fanconi renal tubulopathy syndrome.Journal of nephrology · 2024Article
- Review of childhood genetic nephrolithiasis and nephrocalcinosis.Frontiers in genetics · 2024Review
- When Two Syndromes Collide: Managing Fanconi and Refeeding Syndrome in a Single Patient.Cureus · 2024Article
- Genetic Diagnosis and Treatment of Inherited Renal Tubular Acidosis.Kidney diseases (Basel, Switzerland) · 2023Review
- Expanding the p.(Arg85Trp) Variant-Specific Phenotype of HNF4A: Features of Glycogen Storage Disease, Liver Cirrhosis, Impaired Mitochondrial Function, and Glomerular Changes.Molecular syndromology · 2023Article
- Siblings WithJCEM case reports · 2023Article
- Inherited Fanconi syndrome.World journal of pediatrics : WJP · 2023Review
- Structural insights into the HNF4 biology.Frontiers in endocrinology · 2023Review
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- Syndromic forms of congenital hyperinsulinism.Frontiers in endocrinology · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundMutation 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
resultsWe 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 hypouricaemia, and additional features not seen in Fanconi syndrome: nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcaemia, and hypermagnesaemia. This was mutation specific, with the renal phenotype not being seen in patients with other HNF4A mutations. In silico modelling shows the R76 residue is directly involved in DNA binding and the R76W mutation reduces DNA binding affinity. The target(s) selectively affected by altered DNA binding of R76W that results in Fanconi syndrome is not known.
conclusionsThe HNF4A R76W mutation is an unusual example of a mutation specific phenotype, with autosomal dominant atypical Fanconi syndrome in addition to the established beta cell phenotype.
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