A Family with Autosomal Dominant Distal Renal Tubular Acidosis Presents with Atypical Phenotype Caused by a Missence Mutation (R388C) of the Human Kidney Anion Exchanger

Hereditary forms of distal renal tubular acidosis (dRTA) are rare and mainly caused by mutations in ATP6V1B1, ATP6V0A4 and SLC4A1. About 20 mutations in SLC4A1 gene have been found that are related to either autosomal dominant (AD) or autosomal recessive dRTA. AD dRTA often manifest as constitutional and can easily be delayed in diagnosis and treatment. A 30-year-old male patient has a history of paroxysmal paralysis for 7 years, presenting with mild hypokalemia, alkalization of urine, normal blood PH value and increased urinary calcium. Patient’s father has similar presentations but never came to the hospital. We find a heterozygous mutation (c.1162C>T, p.Arg388Cys) located in exon 11 of SLC4A1 gene by utilization of next-generation sequencing technology. Both patient and his father carry the same mutation. Highly conserved R388 is located in amphipathic helix 1 of N-terminal of the kAE1 protein, which may cause AD dRTA by changing the conformation of kAE1. Expression studies provide evidence that the mutant kAE1 R388C proteins are impaired in trafficking to the cell surface.