title: A novel CLDN16 mutation in a large family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.
abstract: BACKGROUND
  Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is a rare tubulopathy leading to renal calcification and progressive renal failure.
  
  
  METHODS
  We report a consanguineous Arab family (of Qatari origin) with 7 affected siblings with variable phenotypes including hypomagnesaemia, hypercalciuria, nephrocalcinosis and renal stones. Presenting features included haematuria and recurrent urinary tract infections. As the biochemical and clinical phenotypes of this family resembled familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, we performed genetic investigation in order to provide a precise molecular diagnosis. We screened all coding regions of the CLDN16 gene and identified a novel mutation (c.G647A, p.R216H) which was found homozygously in the six severely affected cases, who manifested significant nephrocalcinosis, often nephrolithiasis and sometimes reduced GFR. Parents were both heterozygous for the mutation and, together with children carrying the mutation in its heterozygous state, exhibited mild or no biochemical phenotypes.
  
  
  CONCLUSIONS
  Mutations in CLDN16 underlie familial hypomagnesaemia with hypercalciuria and nephrocalcinosis but remain a rare cause of nephrocalcinosis and nephrolithiasis. Management includes reduction of hypercalciuria with thiazide diuretics, correction of serum magnesium and close monitoring of renal function given the significant risk of end stage renal failure with this inherited form of nephrocalcinosis.
authors: Asma
authors: A
authors: Deeb
authors: Salima Atia
authors: SA
authors: Abood
authors: Job
authors: J
authors: Simon
authors: Hormazdiar
authors: H
authors: Dastoor
authors: Simon Hs
authors: SH
authors: Pearce
authors: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. john.sayer@ncl.ac.uk.
authors: John A
authors: JA
authors: Sayer
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D057167:Claudins / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053565:Hypercalciuria / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007223:Infant; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008274:Magnesium / Q000008:administration & dosage; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D015499:Renal Tubular Transport, Inborn Errors / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use
chemical_list: D057167:Claudins; D049993:Sodium Chloride Symporter Inhibitors; C502010:claudin 16; D008274:Magnesium