title: Identification of two novel mutations in the SLC4A1 gene in two unrelated Chinese families with distal renal tubular acidosis.
abstract: OBJECTIVE
  Distal renal tubular acidosis (dRTA) is characterized by a reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Mutations in the SLC4A1 gene have been found to cause either autosomal dominant (AD) or autosomal recessive (AR) dRTA.
  
  
  METHODS
  Four affected individuals and nine healthy family members from two unrelated Chinese families with dRTA were clinically studied. The SLC4A1 gene was screened and analyzed, and the mutations were confirmed using molecular genetic techniques.
  
  
  RESULTS
  In family1, the affected individuals had novel compound heterozygous SLC4A1 G494S/G701D mutations inherited from their clinically normal heterozygous father and mother, respectively. In family 2, the affected individuals exhibited a novel 3-bp duplication (c.2715_2717dupCGA) in exon 20 of SLC4A1 that led to the D905dup mutation. The age of presentation was younger, hypokalemia was more severe, and growth retardation was more severe in recessive patients in family 1 than patients with AD dRTA in family 2.
  
  
  CONCLUSIONS
  This is the first report of dRTA patients with compound heterozygous conditions in mainland China. Two novel SLC4A1 mutations (G494S and D905dup) were identified. Our results confirm the importance of the C-terminal residues of the SLC4A1 gene product in normal acidification processes and indicate that mutations in this region are likely to result in AD dRTA. Our study extends the mutation spectrum of dRTA and is helpful in early molecular diagnoses of dRTA.
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affliated Sixth People's Hospital, PR China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kang-Xiang
authors.initials: KX
authors.lastname: Liu
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
authors.forename: Hua
authors.initials: H
authors.lastname: Yue
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhang
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000141:Acidosis, Renal Tubular / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D000293:Adolescent; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D002648:Child; D002681:China / Q000453:epidemiology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D006130:Growth Disorders / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D007008:Hypokalemia / Q000209:etiology; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; C454201:SLC4A1 protein, human