Rh. Moseley et al., Downregulated in adenoma gene encodes a chloride transporter defective in congenital chloride diarrhea, AM J P-GAST, 39(1), 1999, pp. G185-G192
Citations number
31
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Congenital chloride diarrhea (CLD) Is a recessively inherited disorder char
acterized by massive loss of chloride in stool. We previously identified mu
tations in the downregulated in adenoma (DRA) gene in patients with CLD and
demonstrated that DRA encodes an intestine-specific sulfate transporter. T
o determine whether DRA is an intestinal chloride transporter and how mutat
ions affect;transport, Xenopus oocytes were injected with wildtype and muta
genized DRA cRNA and uptake of Cl- and SO42- was assayed. Both Cl- and SO42
- were transported by wild-type DRA and an outwardly directed pH gradient s
timulated Cl- uptake, consistent with Cl-/OH- exchange. Among three mutants
, C307W transported both anions as effectively as wild-type, whereas transp
ort activity was lost in V317del and the double mutant identified in 32 of
32 Finnish CLD patients. We conclude that DRA is a chloride transporter def
ective in CLD and that V317del is a functional mutation and C307W a silent
polymorphism.