title: Clustering of private mutations in the congenital chloride diarrhea/down-regulated in adenoma gene.
abstract: An inherited defect in intestinal anion exchange, congenital chloride diarrhea (CLD), was recently shown to be caused by mutations in the down-regulated in adenoma (DRA) gene. A three base pair deletion resulting in the loss of an amino acid valine (V317del) in the predicted CLD/DRA protein was shown to be responsible for all CLD cases in a Finnish founder population. Two additional mutations, H124L and 344delT, were found in Polish CLD patients. Here, we screened for additional mutations in a set of 14 CLD families of Polish, Swedish, North American, and Finnish origin using primers that allowed mutation searches directly from genomic DNA samples. We found eight novel mutations in the CLD/DRA gene. The mutations included two transversions, one transition, one insertion, and four small deletions. Of 11 sequence alterations detected so far, nine lie clustered in three short segments that are 49 bp, 39 bp, and 65 bp in size, respectively. These short segments span only 6.7% of the total cDNA length, suggesting functional importance or mutation-prone DNA regions of the corresponding CLD/DRA protein domains.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland. Pia.Hoglund@Helsinki.Fi
authors.forename: P
authors.initials: P
authors.lastname: Höglund
authors.forename: S
authors.initials: S
authors.lastname: Haila
authors.forename: K H
authors.initials: KH
authors.lastname: Gustavson
authors.forename: M
authors.initials: M
authors.lastname: Taipale
authors.forename: K
authors.initials: K
authors.lastname: Hannula
authors.forename: K
authors.initials: K
authors.lastname: Popinska
authors.forename: C
authors.initials: C
authors.lastname: Holmberg
authors.forename: J
authors.initials: J
authors.lastname: Socha
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: J
authors.initials: J
authors.lastname: Kere
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism*; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D003967:Diarrhea / Q000151:congenital* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000076988:Sulfate Transporters
chemical_list: D017920:Antiporters; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D017931:DNA Primers; D008565:Membrane Proteins; C081011:SLC26A3 protein, human; D000076988:Sulfate Transporters