Compound mutations in human anion exchanger 1 are associated with complete distal renal tubular acidosis and hereditary spherocytosis

Yu Hsiang Chang, Chen Fu Shaw, Shu Huei Jian, Kai Hsien Hsieh, Yee Hsuan Chiou, Pei Jung Lu

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Missense, nonsense, and frameshift mutations in the human anion exchanger 1 have been associated with inherited distal renal tubular acidosis and hereditary spherocytosis. These two disorders, however, are almost always mutually exclusive. We have found an important and unusual exception: a novel combination of heterozygous E522K and G701D mutations in the anion exchanger 1 manifested as complete distal renal tubular acidosis and severe hereditary spherocytosis in an affected patient. Analysis of protein trafficking and subcellular localization of the wild-type kidney isoform of human anion exchanger 1 and these mutants transfected into MDCK cells showed they formed homodimers or heterodimers with each other. Homodimers of the wild-type and E522K mutant were found at the plasma membrane, whereas the G701D mutant largely remained in the cytoplasm. Heterodimers of either E522K or G701D and the wild-type exchanger were located in the plasma membrane, whereas E522K/G701D heterodimers remained in the cytoplasm. Our study shows that the compound E522K/G701D mutation of human anion exchanger 1 causes a trafficking defect in kidney cells, and this may explain the complete distal renal tubular acidosis of the patient.

Original languageEnglish
Pages (from-to)774-783
Number of pages10
JournalKidney international
Volume76
Issue number7
DOIs
Publication statusPublished - 2009 Oct

All Science Journal Classification (ASJC) codes

  • Nephrology

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