title: Nucleotide sequence of the Na+/H+ exchanger-8 in patients with congenital sodium diarrhea.
abstract: Sodium absorption by the intestine is mediated by brush border Na/H exchangers, which include the NHE3 and NHE8 isoforms. We demonstrated a maturational decrease in NHE8 and increase in NHE3 in mouse intestine mRNA abundance and brush border membrane protein abundance, indicating a developmental switch of isoforms. Congenital sodium diarrhea is a rare autosomal recessive disorder characterized by polyhydramnios, hyponatremia, metabolic acidosis, and diarrhea with a high sodium content. Previous studies using intestinal brush border membrane vesicles from patients with this disorder have demonstrated a decrease in Na/H exchanger activity. Because some patients with congenital sodium diarrhea improve with age and knowing the developmental switch from NHE8 to NHE3, NHE8 may be a candidate gene for this disorder. We sequenced NHE8 from 5 patients with this disorder and found no disease-causing homozygous mutations. Although brush border membrane Na/H exchange activity may be decreased, exonic mutations in NHE8 cannot account for this disorder in these subjects.
authors.affiliation: Department of Pediatrics, Mattel Children's Hospital, David Geffen School of Medicine at the University of California, Los Angeles, USA. Michel.Baum@UTSouthwestern.edu
authors.forename: Michel
authors.initials: M
authors.lastname: Baum
authors.forename: Martin G
authors.initials: MG
authors.lastname: Martin
authors.forename: Ian W
authors.initials: IW
authors.lastname: Booth
authors.forename: Christer
authors.initials: C
authors.lastname: Holmberg
authors.forename: Katherine
authors.initials: K
authors.lastname: Twombley
authors.forename: Qiuyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jyothsna
authors.initials: J
authors.lastname: Gattineni
authors.forename: Orson
authors.initials: O
authors.lastname: Moe
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D002648:Child; D003967:Diarrhea / Q000473:pathology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008871:Microvilli / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D012964:Sodium / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C000613385:SLC9A3 protein, human; C486775:SLC9A8 protein, human; C000613386:Slc9a3 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium