ArticleJournal of the American Society of Nephrology : JASN2014
Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BHOrphanet journal of rare diseases · 2020Guideline
- Follow-up and outcome of patients with primary BH4 deficiencies.Frontiers in neurologyPooled it
- Molecular Genetic and Biochemical Characterization of Hyperphenylalaninemia Based on Expanded Neonatal Screening Data from 2023 to 2024 in the Russian Federation.International journal of molecular sciences · 2026Article
- Assessing the causal relationship between the plasma proteome and epilepsy: A Mendelian randomization study.Epilepsia open · 2025Article
- Hepatocyte nuclear factor 1 in renal lipid metabolism: molecular mechanisms and therapeutic potentials.Cell biology and toxicology · 2025Review
- Fuelling the Fight from the Gut: Short-Chain Fatty Acids and Dexamethasone Synergise to Suppress Gastric Cancer Cells.Cancers · 2025Article
- Uncovering glycolysis-driven molecular subtypes in diabetic nephropathy: a WGCNA and machine learning approach for diagnostic precision.Biology direct · 2025Article
- Review
- MODY Only Monogenic? A Narrative Review of theInternational journal of molecular sciences · 2024Review
- An anoikis-related gene signature predicts prognosis, drug sensitivity, and immune microenvironment in cholangiocarcinoma.Heliyon · 2024Article
- Rare cause of recurrent hypocalcaemia and functional hypoparathyroidism due to hypomagnesaemia caused byBMJ case reports · 2024Article
- Magnesium (MgCurrent pharmaceutical design · 2024Review
- Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.Frontiers in molecular biosciences · 2024Article
- Functional genomics analysis identifies loss of HNF1B function as a cause of Mayer-Rokitansky-Küster-Hauser syndrome.Human molecular genetics · 2023Article
- Physiology of a Forgotten Electrolyte-Magnesium Disorders.Advances in kidney disease and health · 2023Review
- Possible role for rare TRPM7 variants in patients with hypomagnesaemia with secondary hypocalcaemia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Genetic regulation of RNA splicing in human pancreatic islets.Genome biology · 2022Article
- Framework From a Multidisciplinary Approach for Transitioning Variants of Unknown Significance From Clinical Genetic Testing in Kidney Disease to a Definitive Classification.Kidney international reports · 2022Article
- Clinical and genetic approach to renal hypomagnesemia.Biomedical journal · 2022Review
- NovelFrontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in PCBD1 are causative for transient neonatal hyperphenylalaninemia and primapterinuria (HPABH4D). Until now, HPABH4D has been regarded as a transient and benign neonatal syndrome without complications in adulthood. In our study of three adult patients with homozygous mutations in the PCBD1 gene, two patients were diagnosed with hypomagnesemia and renal Mg(2+) loss, and two patients developed diabetes with characteristics of maturity onset diabetes of the young (MODY), regardless of serum Mg(2+) levels. Our results suggest that these clinical findings are related to the function of PCBD1 as a dimerization cofactor for the transcription factor HNF1B. Mutations in the HNF1B gene have been shown to cause renal malformations, hypomagnesemia, and MODY. Gene expression studies combined with immunohistochemical analysis in the kidney showed that Pcbd1 is expressed in the distal convoluted tubule (DCT), where Pcbd1 transcript levels are upregulated by a low Mg(2+)-containing diet. Overexpression in a human kidney cell line showed that wild-type PCBD1 binds HNF1B to costimulate the FXYD2 promoter, the activity of which is instrumental in Mg(2+) reabsorption in the DCT. Of seven PCBD1 mutations previously reported in HPABH4D patients, five mutations caused proteolytic instability, leading to reduced FXYD2 promoter activity. Furthermore, cytosolic localization of PCBD1 increased when coexpressed with HNF1B mutants. Overall, our findings establish PCBD1 as a coactivator of the HNF1B-mediated transcription necessary for fine tuning FXYD2 transcription in the DCT and suggest that patients with HPABH4D should be monitored for previously unrecognized late complications, such as hypomagnesemia and MODY diabetes.
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