Background: Distal renal tubular acidosis (dRTA) with hearing impairment is an inherited disease caused by mutations in the ATP6V1B1 or ATP6V0A4 genes encoding ATPase subunits of a proton pump. Clinical manifestations for dRTA include metabolic acidosis , hypokalemia , alkaline urine, nephrocalcinosis and progressive hearing impairment.

Objective: To identify the genetic cause of two patients with dRTA in a Sudanese cohort.

Methods: Two genetically related Sudanese children presented with metabolic acidosis, hypokalemia, nephrocalcinosis , and rickets in a clinic in Khartoum, Sudan. One child was found having sensorineural deafness, which occurs in one third of patients with inherited dRTA. The genetically related parents of both children did not have any symptoms. Following whole exome sequencing on whole-blood derived DNA and quality control steps, Spotfire software (http://spotfire.tibco.com) was used to screen for potential variants.

Results: The variant shared by both patients, located in the gene ATP6V1B1, was identified as a nonsynonymous single nucleotide variation (rs114234874; G/A) in exon 6 with an allele frequency of 0.02-0.03 in the total and African population (Exac browser, http://exac.broadinstitute.org/). Various other selection criteria were used including autosomal inheritance pattern , high conservation (CADD score 18.8) and damage score (varied from tolerant to damaging depending on the tool used).

Conclusions: The variant found in the two children has never been reported before in patients with dRTA. Despite not being identified as a mutation (MAF > 0.01), the potential pathogenic nature of the variant may be responsible for dRTA in the two patients but requires further study in a larger population and supported by fundamental studies.