LAUSR

AIM To analyze the variants of the potential causative genes in five Chinese patients with primary distal renal tubular acidosis (dRTA) from five unrelated families, and to explore their possible genotype-phenotype correlations, so as to raise the awareness of the disease. METHODS Variants were identified by next generation sequencing. Clinical features and biochemical findings at the first presentation, as well as at follow-up visits were also investigated. One hundred unrelated healthy subjects were selected to evaluate each of the novel mutations found in this study. RESULTS A total of seven different mutations in the ATP6V0A4, ATP6V1B1, and SLC4A1 genes, the three main causative genes of dRTA, were detected in 4/5 patients. In patient I a novel heterozygous intronic mutation (c.639 + 1G>A) in the ATP6V0A4 gene was identified along with a heterozygous nonsense variant (c.580C>T, p.Arg194*). Two novel heterozygous missense mutations of the ATP6V1B1 gene (c.409C>T, p.Pro137Ser; c.904C>T, p.Arg302Trp) were identified in patient II. In patient III 2 novel heterozygous duplications (c.1504dupT, p.Tyr502Leufs*22; c.2351dupT, p.Phe785Ilefs*28) were found. Thus, these three patients all were compound heterozygotes leading to dRTA. These findings are consistent with the known autosomal recessive inheritance pattern of this disease. Furthermore, a de novo heterozygous missense mutation previously reported (c.1765C>A, p.Arg589Ser) in the SLC4A1 gene was observed in patient IV. No mutations in any of the known dRTA-related causative genes were found in the patient V. CONCLUSIONS In the present study we identified 7 mutations, including 5 novel variants, in the three genes previously correlated with dRTA, enriching the human gene mutation database (HGMD). In addition, our lack of findings in these three genes for patient V suggests that other genes may contribute to dRTA in some cases.