LAUSR

AIM OF THE STUDY Recent advances in understanding the underlying molecular mechanism for distal renal tubular acidosis (dRTA), led to an increased attention towards the primary and the familial forms of the disease. Mutations in ATP6V1B1 and ATP6V0A4 are usually responsible for the recessive form of the disease. Mutations in gene AE1 encoding the Cl-/HCO3- exchanger, usually present as dominant dRTA, but a recessive pattern has been recently described. Our objective is to identify the mutational spectrum responsible of dRTA in a consanguineous Libyan family. MATERIALS AND METHODS Both ATP6V0A4 and ATP6V1B1 genes were preferentially screened in our patient. Additional whole exome sequencing (WES) in the same patient, offered a wider view on potential chromosomal rearrangements as well as the mutational spectrum of other genes involved in this disease. RESULTS The patient is a heterozygote for two different mutations, one in each of the genes ATP6V0A4 and ATP6V1B1, while no deleterious variation was detected in the remaining genes responsible for the recessive form of dRTA. Homozygosity mapping and WES confirmed our findings and supported the hypothesis of a digenic inheritance model existing as an explanation for dRTA. CONCLUSIONS To our knowledge, this is the first report describing a Libyan patient with dRTA who suffered from early-onset sensorineural hearing loss, with a digenic mode of inheritance, supported by the identification of two novel mutations. This study increases the understanding of how dRTA is genetically transmitted, while offers a good outline towards the molecular diagnostics and genetic counseling for dRTA in Lybians.