학술논문
Mutations in the gene encoding B1 subunit of H+ -ATPase cause renal tubular acidosis with sensorineural deafness.
Document Type
Article
Author
Karet, Fiona E.; Finberg, Karin E.; Nelson, Raoul D.; Nayir, Ahmet; Mocan, Hilal; Sanjad, Sami A.; Rodriguez-Soriano, Juan; Santos, Fernando; Cremers, Cor W.R.J.; Pietro, Antonio Di; Hoffbrand, Barry I.; Winiarski, Jacek; Bakkaloglu, Aysin; Ozen, Seza; Dusunsel, Ruhan; Goodyer, Paul; Hulton, Sally A.; Wu, Doris K.; Skvorak, Anne B.
Source
Subject
*GENETIC mutation
*ACIDOSIS
*SENSORINEURAL hearing loss
*HOMEOSTASIS
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Language
ISSN
1061-4036
Abstract
H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease. [ABSTRACT FROM AUTHOR]