Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness

F E Karet; K E Finberg; R D Nelson; A Nayir; H Mocan; S A Sanjad; J Rodriguez-Soriano; F Santos; C W Cremers; A Di Pietro; B I Hoffbrand; J Winiarski; A Bakkaloglu; S Ozen; R Dusunsel; P Goodyer; S A Hulton; D K Wu; A B Skvorak; C C Morton; M J Cunningham; V Jha; R P Lifton

doi:10.1038/5022

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness

F E Karet, K E Finberg, R D Nelson, A Nayir, H Mocan, S A Sanjad, J Rodriguez-Soriano, F Santos, C W Cremers, A Di Pietro, B I Hoffbrand, J Winiarski, A Bakkaloglu, S Ozen, R Dusunsel, P Goodyer, S A Hulton, D K Wu, A B Skvorak, C C MortonM J Cunningham, V Jha, R P Lifton

Division of Evolution, Infection and Genomics

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	84-90
Number of pages	7
Journal	Nature Genetics
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/5022
Publication status	Published - Jan 1999

Keywords

Acidosis, Renal Tubular
Base Sequence
Child, Preschool
Chromosomes, Human, Pair 2
Cochlea
Female
Genes, Recessive
Genetic Linkage
Hearing Loss, Sensorineural
Humans
Infant
Male
Molecular Sequence Data
Mutation
Pedigree
Proton-Translocating ATPases
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

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Karet, F. E., Finberg, K. E., Nelson, R. D., Nayir, A., Mocan, H., Sanjad, S. A., Rodriguez-Soriano, J., Santos, F., Cremers, C. W., Di Pietro, A., Hoffbrand, B. I., Winiarski, J., Bakkaloglu, A., Ozen, S., Dusunsel, R., Goodyer, P., Hulton, S. A., Wu, D. K., Skvorak, A. B., ... Lifton, R. P. (1999). Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness. Nature Genetics, 21(1), 84-90. https://doi.org/10.1038/5022

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title = "Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness",

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.",

keywords = "Acidosis, Renal Tubular, Base Sequence, Child, Preschool, Chromosomes, Human, Pair 2, Cochlea, Female, Genes, Recessive, Genetic Linkage, Hearing Loss, Sensorineural, Humans, Infant, Male, Molecular Sequence Data, Mutation, Pedigree, Proton-Translocating ATPases, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.",

author = "Karet, {F E} and Finberg, {K E} and Nelson, {R D} and A Nayir and H Mocan and Sanjad, {S A} and J Rodriguez-Soriano and F Santos and Cremers, {C W} and {Di Pietro}, A and Hoffbrand, {B I} and J Winiarski and A Bakkaloglu and S Ozen and R Dusunsel and P Goodyer and Hulton, {S A} and Wu, {D K} and Skvorak, {A B} and Morton, {C C} and Cunningham, {M J} and V Jha and Lifton, {R P}",

year = "1999",

month = jan,

doi = "10.1038/5022",

language = "English",

volume = "21",

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journal = "Nature Genetics",

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Karet, FE, Finberg, KE, Nelson, RD, Nayir, A, Mocan, H, Sanjad, SA, Rodriguez-Soriano, J, Santos, F, Cremers, CW, Di Pietro, A, Hoffbrand, BI, Winiarski, J, Bakkaloglu, A, Ozen, S, Dusunsel, R, Goodyer, P, Hulton, SA, Wu, DK, Skvorak, AB, Morton, CC, Cunningham, MJ, Jha, V & Lifton, RP 1999, 'Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness', Nature Genetics, vol. 21, no. 1, pp. 84-90. https://doi.org/10.1038/5022

TY - JOUR

T1 - Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness

AU - Karet, F E

AU - Finberg, K E

AU - Nelson, R D

AU - Nayir, A

AU - Mocan, H

AU - Sanjad, S A

AU - Rodriguez-Soriano, J

AU - Santos, F

AU - Cremers, C W

AU - Di Pietro, A

AU - Hoffbrand, B I

AU - Winiarski, J

AU - Bakkaloglu, A

AU - Ozen, S

AU - Dusunsel, R

AU - Goodyer, P

AU - Hulton, S A

AU - Wu, D K

AU - Skvorak, A B

AU - Morton, C C

AU - Cunningham, M J

AU - Jha, V

AU - Lifton, R P

PY - 1999/1

Y1 - 1999/1

N2 - 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.

AB - 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.

KW - Acidosis, Renal Tubular

KW - Base Sequence

KW - Child, Preschool

KW - Chromosomes, Human, Pair 2

KW - Cochlea

KW - Female

KW - Genes, Recessive

KW - Genetic Linkage

KW - Hearing Loss, Sensorineural

KW - Humans

KW - Infant

KW - Male

KW - Molecular Sequence Data

KW - Mutation

KW - Pedigree

KW - Proton-Translocating ATPases

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1038/5022

DO - 10.1038/5022

M3 - Article

C2 - 9916796

SN - 1061-4036

VL - 21

SP - 84

EP - 90

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness

Abstract

Keywords

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