SLC26A3 mutations in congenital chloride diarrhea

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder of intestinal electrolyte absorption. It is characterized by persistent secretory diarrhea resulting in polyhydramnios and prematurity prenatally, and dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive immediately after birth. CLD is caused by mutations in the solute carrier family 26, member 3 gene (SLC26A3, alias CLD or DRA), which encodes a Na + ‐independent Cl − /HCO 3 − (or OH − ) exchanger. SLC26A3 is a member of the SLC26 sulfate permease/anion transporter family and it is expressed mainly in the apical brush border of intestinal epithelium. The only extraintestinal tissues showing SLC26A3 expression are eccrine sweat glands and seminal vesicles. A wide variety of different mutations in the SLC26A3 gene have been associated with CLD with no apparent evidence of phenotype–genotype correlation. The clinical course of CLD, however, is variable and may rather depend on environmental factors and compensatory mechanisms than mutations. In this report, we present a summary of all published and two novel SLC26A3 mutations and polymorphisms, and review them in the context of their functional consequences and clinical implications. Hum Mutat 20:425–438, 2002. © 2002 Wiley‐Liss, Inc.