Clinical features and genetic findings in Chinese children with distal renal tubular acidosis.

: Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis due to uric acid dysfunction. The aim of this study was to demonstrate the genetic diagnosis of Chinese children with dRTA by whole-exome sequencing. From Jan. 2010 to Sept. 2015, 16 children with dRTA were recruited to investigate the possibility of genetic diagnosis and to examine any genotype-phenotype relationships in these patients. Sanger sequencing was used to confirm mutations identified by whole-exome sequencing. Clinical and biological features in the patients included hyperchloremic metabolic acidosis, impaired growth, hypokalemia, nephrocalcinosis, nephrolithiasis, hypercalciuria, hypocitraturia, and rickets or osteomalacia. Seventeen mutations in the solute carrier family 4 member 1 (SLC4A1), ATPase H+ transporting V0 subunit a4 (ATP6V0A4), ATPase H+ transporting V1 subunit B1 (ATP6V1B1), WNK lysine deficient protein kinase 1 (WNK1) and the claudin 16 (CLDN16) were identified in 15 patients, and 14 of these mutations are novel. Only 1 patient was negative for any mutations. Our results demonstrate the existence of SLC4A1, ATP6V1B1, ATP6V0A4, WNK1 and CLDN16 mutations in Chinese children with dRTA and indicate that compound heterozygosity at 2 or more different but related genes can be responsible for its pathogenesis. This study also indicates that whole-exome sequencing is a labor and cost-effective means of analyzing dRTA-associated genes.