Clinical and molecular findings in three Moroccan families with distal renal tubular acidosis and deafness: Report of a novel mutation of ATP6V1B1 gene

Abstract

Background: Primary distal renal tubular acidosis (dRTA) is a rare genetic condition characterized by an impaired acid excretion by the intercalated cells in the renal collecting duct. Recessive forms of this disease are caused by mutations in tow major genes: ATP6V1B1 and ATP6V0A4. Causal mutations in ATP6V1B1 gene are classically associated with early sensorineural hearing loss, however cases of tubular acidosis with early deafness have also been described in patients with mutations in the ATP6V0A4 gene.

Methods: The phenotype and genotype of three Moroccan consanguineous families with dRTA and deafness were assessed. Molecular analysis was performed by PCR amplification and direct sequencing of exon 12 of ATP6V1B1 gene.

Results: A novel c.1169dupC frameshift mutation of ATP6V1B1 gene was identified in one family and the c.1155dupC North African mutation in the tow other families.

Discussion and conclusion: In this report, we propose first line genetic testing based on screening of these two mutations both located in exon 12 of ATP6V1B1 gene in Moroccan patients with recessive form of dRTA associated to precocious hearing loss. Molecular diagnosis of dRTA leads to appropriate treatment and prevention of renal failure in affected individuals and to provide genetic counseling for families at risk.

Keywords: ATP6V1B1 gene; Autosomal recessive; Moroccan; Mutation; Renal tubular acidosis; Sensorineural deafness.