A novel de novo SLC26A3 mutation causing congenital chloride diarrhea in a Japanese neonate

BACKGROUND: Congenital chloride diarrhea (CCD) is characterized by persistent chloride (Cl)‐rich diarrhea evident from birth. CCD is a rare autosomal recessive disorder caused by defects in the solute carrier family 26 member 3 (SLC26A3) gene, which encodes an intestinal Cl(−)/HCO3(−), Na(+)‐independent exchanger. Various mutations of SLC26A3 have been described in CCD. However, no de novo mutations have been found to be responsible for CCD. Here we report the first such occurrence. METHODS: Clinical and laboratory findings during the perinatal period were obtained retrospectively from medical records. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: The male infant reported here was delivered at 29 weeks of gestation. Just after birth, he had watery diarrhea without meconium passage. High chloride concentrations in the diarrhea led to a diagnosis of CCD. Direct sequencing of all coding exons in SLC26A3 including exon‐intron boundaries disclosed 2 compound heterozygous mutations: c.382G>A, p.G128S and c.2063‐1g>t. The c. 2063‐1g>t mutation was confirmed in his mother's DNA, but c.382G>A, p.G128S was absent in both mother and father. CONCLUSION: We concluded that c.382G>A, p.G128S represented a de novo mutation of SLC26A3, a very rare event in autosomal recessive disorders. To our knowledge, this is the first CCD case involving a de novo novel mutation of SLC26A3.