title: Autosomal recessive distal renal tubular acidosis caused by G701D mutation of anion exchanger 1 gene.
abstract: Anion exchanger 1 (AE1 or band 3), encoded by the AE1 or SLC4A1 gene, regulates chloride-bicarbonate exchange in erythrocytes and alpha-intercalated cells of the distal nephron. Defects of AE1 at the basolateral membrane of alpha-intercalated cells may result in the failure of hydrogen ion secretion at the apical membrane, leading to distal renal tubular acidosis (dRTA). Abnormalities of the AE1 gene were previously reported to be associated with autosomal dominant dRTA. However, recent studies of Thai dRTA families have shown that mutations in this gene result in autosomal recessive (AR) dRTA, giving rise to the postulation that AE1 gene mutations causing AR dRTA might be found commonly in Thai pediatric patients with dRTA. We performed a study of the AE1 gene using DNA linkage, polymerase chain reaction single-strand conformation polymorphism, restriction endonuclease HpaII digestion, and DNA sequence analyses in eight families involving 12 Thai children with dRTA, shown by abnormal urinary acidification using a short acid-loading test, as well as among their family members. Seven patients with dRTA from five families had the same homozygous missense G701D mutation of the AE1 gene. Their parents or siblings heterozygous for the AE1 G701D mutation were clinically normal and did not have abnormal urinary acidification, although a heterozygous sibling in one family had abnormal urinary acidification. Results of this and previous studies show that a homozygous AE1 G701D mutation causes AR dRTA and is a common molecular defect among Thai pediatric patients with dRTA.
authors.affiliation: Division of Medical Molecular Biology, Department of Research and Development, Renal Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. grpye@mahidol.ac.th
authors.forename: Pa-thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: Somkiat
authors.initials: S
authors.lastname: Vasuvattakul
authors.forename: Sukachart
authors.initials: S
authors.lastname: Kirdpon
authors.forename: Sirijitta
authors.initials: S
authors.lastname: Wasanawatana
authors.forename: Wattanachai
authors.initials: W
authors.lastname: Susaengrat
authors.forename: Suchai
authors.initials: S
authors.lastname: Sreethiphayawan
authors.forename: Duangporn
authors.initials: D
authors.lastname: Chuawatana
authors.forename: Sumitra
authors.initials: S
authors.lastname: Mingkum
authors.forename: Nunghathai
authors.initials: N
authors.lastname: Sawasdee
authors.forename: Peti
authors.initials: P
authors.lastname: Thuwajit
authors.forename: Prapon
authors.initials: P
authors.lastname: Wilairat
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.forename: Sumalee
authors.initials: S
authors.lastname: Nimmannit
mesh_terms: D000141:Acidosis, Renal Tubular / Q000209:etiology* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006580:Genetic Carrier Screening; D005820:Genetic Testing / Q000379:methods; D005998:Glycine / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009679:Nuclear Family; D010375:Pedigree; D013785:Thailand / Q000453:epidemiology
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D001224:Aspartic Acid; D005998:Glycine