title: Clinical and molecular characterization of Turkish patients with familial hypomagnesaemia: novel mutations in TRPM6 and CLDN16 genes.
abstract: BACKGROUND
  Recent identification and characterization of novel renal Mg(2+) transporters and ion channels have greatly increased our understanding of the normal physiology of renal magnesium handling.
  
  
  METHODS
  The present study deals with the clinical and molecular characterization of eight Turkish children (median age 10.6 years, range 3-16.2 years, five boys and three girls) with primary hypomagnesaemia from six families.
  
  
  RESULTS
  All patients initially presented with tetany and convulsions. Laboratory evaluation yielded severely low serum magnesium levels and low serum calcium levels in all patients. While six patients exhibited inadequately low parathyroid hormone levels, the two remaining patients showed hyperparathyroidism, hypercalciuria and nephrocalcinosis. Genetic studies revealed familial hypomagnesaemia with secondary hypocalcaemia (HSH) due to a TRPM6 mutation in six patients and familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) due to a CLDN16 mutation in one patient.
  
  
  CONCLUSIONS
  Among recently identified magnesium-wasting disorders, HSH and FHHNC represent two major entities also in the Turkish population. Besides clinical course and laboratory diagnosis of hypomagnesaemia, the detection of renal calcium wasting and parathyroid function are crucial to differentiate between these most prevalent forms of hereditary magnesium deficiency. While TRPM6 mutations underlying HSH almost uniformly lead to a complete loss of function of the TRPM6 protein, the severity of FHHNC phenotype depends on the residual function of the mutated claudin-16 protein.
authors.affiliation: Department of Paediatrics, Division of Paediatric Endocrinology, Marmara University Hospital, Istanbul, Turkey.
authors.forename: Tulay
authors.initials: T
authors.lastname: Guran
authors.forename: Teoman
authors.initials: T
authors.lastname: Akcay
authors.forename: Abdullah
authors.initials: A
authors.lastname: Bereket
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Atay
authors.forename: Serap
authors.initials: S
authors.lastname: Turan
authors.forename: Lea
authors.initials: L
authors.lastname: Haisch
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.forename: Karl P
authors.initials: KP
authors.lastname: Schlingmann
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D057167:Claudins / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053565:Hypercalciuria / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015499:Renal Tubular Transport, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D050053:TRPM Cation Channels / Q000235:genetics*; D014421:Turkey / Q000453:epidemiology
chemical_list: D057167:Claudins; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; C502010:claudin 16