title: Significance of molecular testing for congenital chloride diarrhea.
abstract: OBJECTIVE
  Autosomal recessive, congenital chloride diarrhea (CLD) is a form of persistent secretory diarrhea, presenting with polyhydramnios and intractable diarrhea from birth. CLD is caused by mutations in the SLC26A3 gene, encoding a Na+-independent Cl/HCO3- exchanger. The diagnosis is generally made on the basis of high fecal chloride concentration in patients with serum electrolyte homoeostasis corrected by salt substitution. We aimed to evaluate the role of diagnostic genetic testing in CLD.
  
  
  METHODS
  Clinical and laboratory data were collected from 8 unrelated children diagnosed as having or suspected to have CLD. The evaluation included physical examination, routine clinical chemistry, and SLC26A3 mutation analysis by direct sequencing of DNA extracted from buccal swabs or peripheral leukocytes.
  
  
  RESULTS
  CLD was initially diagnosed on high fecal chloride concentrations in 7 patients, and by mutation analysis in 1 patient. In 3 of these patients the correct diagnosis was made more than 6 months after birth. We identified SLC26A3 mutations on both alleles in all 8 patients with CLD, including 3 novel missense and 4 novel truncating mutations. We present a compilation of reported SLC26A3 mutations and polymorphisms.
  
  
  CONCLUSIONS
  The diagnosis and therapy of CLD were considerably delayed in 3 of 8 patients from this series, highlighting the potential of misdiagnosing CLD. We add 7 novel mutations, including 3 missense changes of highly conserved residues to a total of 41 mutations in this gene. Molecular analysis is efficient and should be considered as a means of early diagnosis of CLD, especially if the clinical diagnosis remains uncertain.
authors.affiliation: Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lechner
authors.forename: Frank M
authors.initials: FM
authors.lastname: Ruemmele
authors.forename: Andreas
authors.initials: A
authors.lastname: Zankl
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Lausch
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Huber
authors.forename: Walter
authors.initials: W
authors.lastname: Mihatsch
authors.forename: Alan D
authors.initials: AD
authors.lastname: Phillips
authors.forename: Peter
authors.initials: P
authors.lastname: Lewindon
authors.forename: Uwe
authors.initials: U
authors.lastname: Querfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Heinz-Erian
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D027963:Chloride-Bicarbonate Antiporters / Q000737:chemistry / Q000235:genetics*; D002712:Chlorides / Q000032:analysis; D004252:DNA Mutational Analysis; D030562:Databases, Protein; D057210:Delayed Diagnosis / Q000517:prevention & control; D003967:Diarrhea / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics*; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D000076988:Sulfate Transporters
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D050505:Mutant Proteins; C081011:SLC26A3 protein, human; D000076988:Sulfate Transporters