While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and hypomagnesemia.
We retrospectively reviewed radiographic and laboratory data for all patients from a single center who had been screened for an HNF1B mutation.
We found heterozygous mutations in 21 (23%) of 91 cases of renal malformation.
All mutation carriers had abnormal fetal renal ultrasonography.
Plasma magnesium levels were available for 66 patients with chronic kidney disease (stages 1 to 3). Striking, 44% (eight of 18) of mutation carriers had hypomagnesemia (<1.58 mg/dl) compared with 2% (one of 48) of those without mutations (P < 0.0001). The median plasma magnesium was significantly lower among mutation carriers than those without mutations (1.68 versus 2.02 mg/dl; P < 0.0001). Because hypermagnesuria and hypocalciuria accompanied the hypomagnesemia, we analyzed genes associated with hypermagnesuria and detected highly conserved HNF1 recognition sites in FXYD2, a gene that can cause autosomal dominant hypomagnesemia and hypocalciuria when mutated.
Using a luciferase reporter assay, we demonstrated HNF1B-mediated transactivation of FXYD2. These results extend the phenotype of HNF1B mutations to include hypomagnesemia. HNF1B regulates transcription of FXYD2, which participates in the tubular handling of Mg(2+), thus describing a role for HNF1B not only in nephrogenesis but also in the maintenance of tubular function.
- DOI - Journal of the American Society of Nephrology : JASN (DOI)
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JournalJournal of the American Society of Nephrology
J Am Soc Nephrol (1533-3450)
Journal of the American Society of Nephrology : JASN
Nephrology Unit, Great Ormond Street Hospital NHS Trust, London WCIN 3JH, UK.
J Am Soc Nephrol. 2009 May;20(5):1123-31
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