title: Cation-leak stomatocytosis in standard schnauzers does not cosegregate with coding mutations in the RhAG, SLC4A1, or GLUT1 genes associated with human disease.
abstract: Autosomal dominant overhydrated cation-leak stomatocytosis in humans has been associated with missense mutations in the erythroid membrane transport genes AE1, RhAG, and GLUT1. Syndromic stomatocytosis has been reported in three dog breeds, but stomatocytosis in Standard Schnauzers is usually asymptomatic, and is accompanied by minimal if any anemia. We have extended the evaluation of a cohort of schnauzers. We found that low-level stomatocytosis was accompanied by increased MCV and increased red cell Na content, and minimal or no reticulocytosis. Red cells from two affected dogs exhibited increased currents in on-cell patches measured in symmetrical NaCl solutions, but Na,K-ATPase and NKCC-mediated cation flux was minimal. Three novel coding polymorphisms found in canine RhAG cDNA and three novel polymorphisms found in canine SLC4A1 cDNA did not cosegregate with MCV or Na content. The GLUT1 cDNA sequence was normal. We conclude that unlike human overhydrated cation-leak stomatocytosis, stomatocytosis in this cohort of Standard Schnauzers is not caused by mutations in the genes encoding RhAG, SLC4A1, or GLUT1.
authors.affiliation: Dept. of Medicine, Beth Israel Deaconess Med. Ctr, Boston, MA 02215, United States.
authors.forename: Boris E
authors.initials: BE
authors.lastname: Shmukler
authors.forename: Alicia
authors.initials: A
authors.lastname: Rivera
authors.forename: David H
authors.initials: DH
authors.lastname: Vandorpe
authors.forename: Jessica
authors.initials: J
authors.lastname: Alves
authors.forename: Ugo
authors.initials: U
authors.lastname: Bonfanti
authors.forename: Saverio
authors.initials: S
authors.lastname: Paltrinieri
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
mesh_terms: D000745:Anemia, Hemolytic, Congenital / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D001692:Biological Transport; D002412:Cations / Q000378:metabolism; D004285:Dogs; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D007477:Ions / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D002412:Cations; D051272:Glucose Transporter Type 1; D007477:Ions; D008562:Membrane Glycoproteins