Identification of SLC26A3 mutations in a Korean patient with congenital chloride diarrhea

Abstract

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder with the hallmark of persistent watery Cl(-)-rich diarrhea from birth. Mutations in the solute carrier family 26, member 3 (SLC26A3) gene, which encodes a coupled Cl(-)/HCO(3)(-) exchanger in the ileum and colon, are known to cause CLD. Although there are a few reports of CLD patients in Korea, none of these had been confirmed by genetic analysis. Here, we describe the case of a Korean infant with clinical features of CLD. Using direct sequencing analysis, we identified 2 sequence variants: a missense variant of unknown significance (c.525G>C; p.Arg175 Ser) and a splicing mutation (c.2063-1G>T) in the SLC26A3 gene; these had been inherited from the father and mother, respectively. Whilst CLD is rare, its main symptom, diarrhea, is very common in infants. Hence, the diagnosis of CLD can prove difficult. Mutational analysis of the SLC26A3 gene should be considered as a viable method to confirm a diagnosis of CLD in Korean infants with persistent diarrhea.

Keywords: Congenital chloride diarrhea; Mutation; SLC26A3 gene.

Fig. 1

Simple abdominal radiography showing marked dilatation of bowel loops.

Fig. 2

Sequence analysis of the SLC26A3 gene. The patient had a compound heterozygous missense variant in exon 5 (c.525G>C; p.Arg 175Ser) and a splicing mutation in intron 18 (c.2063-1G>T); the father and mother were heterozygous carriers of each of the variants, respectively. Arrows indicate the variant sequences.