ATP6B1 gene mutations associated with distal renal tubular acidosis and deafness in a child

doi:10.1053/ajkd.2003.50014

American Journal of Kidney Diseases

Volume 41, Issue 1, January 2003, Pages 238-243

https://doi.org/10.1053/ajkd.2003.50014 Get rights and content

Abstract

A large proportion of autosomal recessive distal renal tubular acidosis (RTA) is associated with mutations in the ATP6B1 gene encoding the B1 subunit of H⁺-ATPase. H⁺-ATPase is one of the key membrane transporters for net acid excretion in the α-intercalated cells of the medullary collecting duct. Sensorineural hearing loss frequently accompanies this type of distal RTA. Mutational analysis of the ATP6B1 gene in a 9-year-old Korean boy with distal RTA and sensorineural hearing loss found 2 heterozygous missense point mutations. Although a single case report, this is the second report documenting ATP6B1 mutations in recessive distal RTA with sensorineural hearing loss after the original report by Karet et al and confirms the novelty of these mutations. Am J Kidney Dis 41:238-243. © 2003 by the National Kidney Foundation, Inc.

Section snippets

Case report

A 2-month-old Korean boy was referred because of frequent vomiting and failure to thrive. Born at 38 weeks' gestation with a birth weight of 4.1 kg, he was the fourth child of nonconsanguineous parents. The antenatal and perinatal history was unremarkable. His sucking power had been poor, and weight gain was negligible after birth, accompanied by the development of severe vomiting at the age of 2 months. At presentation, his weight was 3.9 kg (below 3 percentiles) and height was 52 cm (below 3

Discussion

The primary and hereditary forms of renal tubular transport disorders including distal RTA are rare. However, recent molecular biological work has drawn much academic attention to these entities by opening a new perspective for the understanding of their molecular pathophysiology.

The kidneys normally respond to acidemia by reabsorbing all of the filtered bicarbonate and increasing hydrogen excretion primarily via enhancement of urinary ammonium excretion. The former response is mainly a

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Cited by (30)

Renal Tubular Acidosis
2019, Pediatric Clinics of North America
Citation Excerpt :
In (young) children presenting with type 1 RTA, single gene defects should be considered. Not surprisingly, given its requirement for the acidification of urine, mutations in 2 of the subunits of the plasma membrane H+ATPase, α4 (gene name ATPV0A4) and β1 (gene name ATPV1B1) or the anion exchanger isoform 1, AE1 (gene name SLC4A1) can cause isolated dRTA.34–40 Mutation in carbonic anhydrase isoform 2 (gene name CA2) results in a mixed picture of both proximal renal tubular acidosis (pRTA) and dRTA.14
Clinical and molecular findings in three Moroccan families with distal renal tubular acidosis and deafness: Report of a novel mutation of ATP6V1B1 gene
2016, Current Research in Translational Medicine
Citation Excerpt :
The apical H+-ATPase of the α-intercalated cells is composed of multiple subunits and responsible for urine acidification. Distal renal tubular acidosis is due to impairment of this function leading to sever metabolic acidosis and altered bone physiology and growth [12,16]. The original disease genetic description made by Karet et al. in 1999 reported that in families with dRTA and early-onset hearing loss, the putative mutations were identified in ATP6V1B1 gene encoding the B subunit of the H+-ATPase pump, while ATP6V0A4 gene which encodes for another subunit of this pump named A4 was implicated in dRTA with normal hearing or at least older-onset hearing impairment [6,9,17].
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.
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.
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.
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.
Renal tubular acidosis
2014, Journal of Pediatrics
Citation Excerpt :
Nerve deafness is present in both autosomal recessive forms of dRTA caused by defective H+ATPase, but not in patients with an AE1 mutation. The age at which hearing impairment begins ranges from the first months of life to age 15 years, although most patients experience hearing impairment before age 12 years.21,46-49 Bilateral enlargement of the vestibular aqueduct has been reported in some deaf patients with dRTA.50
Structure of the yeast vacuolar ATPase
2008, Journal of Biological Chemistry
The subunit architecture of the yeast vacuolar ATPase (V-ATPase) was analyzed by single particle transmission electron microscopy and electrospray ionization (ESI) tandem mass spectrometry. A three-dimensional model of the intact V-ATPase was calculated from two-dimensional projections of the complex at a resolution of 25 Å. Images of yeast V-ATPase decorated with monoclonal antibodies against subunits A, E, and G position subunit A within the pseudo-hexagonal arrangement in the V₁, the N terminus of subunit G in the V₁-V₀ interface, and the C terminus of subunit E at the top of the V₁ domain. ESI tandem mass spectrometry of yeast V₁-ATPase showed that subunits E and G are most easily lost in collision-induced dissociation, consistent with a peripheral location of the subunits. An atomic model of the yeast V-ATPase was generated by fitting of the available x-ray crystal structures into the electron microscopy-derived electron density map. The resulting atomic model of the yeast vacuolar ATPase serves as a framework to help understand the role the peripheral stalk subunits are playing in the regulation of the ATP hydrolysis driven proton pumping activity of the vacuolar ATPase.
Hereditary renal tubular acidosis
2008, Molecular and Genetic Basis of Renal Disease
Hereditary renal tubular acidosis
2007, Molecular and Genetic Basis of Renal Disease: A Companion to Brenner and Rector's The Kidney

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: Supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (HMP-00-B-21000-0032) and 2002 BK21 project for Medicine, Dentistry and Pharmacy.

: Address reprint requests to Hae Il Cheong, MD, Department of Pediatrics, Seoul National University Children's Hospital, 28 Yongon-Dong, Chongro-Gu, Seoul 110-744, Korea. E-mail: [email protected]

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Case ReportsATP6B1 gene mutations associated with distal renal tubular acidosis and deafness in a child★

Abstract

Section snippets

Case report

Discussion

J Biol Chem

Am J Kidney Dis

Kidney Int

FEBS Lett

Am J Kidney Dis

Am J Hum Genet

Am J Kidney Dis

J Pediatr

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

Nat Genet

Evidence for autosomal recessive inheritance of the syndrome of renal tubular acidosis with deafness

Birth Defects Orig Artic Ser

Renal Tubular acidosis and nerve deafness

Arch Dis Child

Siblings with renal tubular acidosis and nerve deafness. The first family in Japan

Human Genet

Long-term follow-up in distal renal tubular acidosis with sensorineural deafness

Pediatr Nephrol

Electrophysiological identification of principal and intercalated cells in the rabbit outer medullary collecting duct

Eur J Physiol

Function and regulation of collecting duct intercalated cells

Annu Rev Physiol

Selectively amplified expression of an isoform of the vacuolar H+ ATPase 56-kilodalton subunit in renal intercalated cells

Proc Natl Acad Sci U S A

An H+ ATPase in opposite plasma membrane domains in kidney epithelial cell subpopulations

Nature

Characterization of K-ATPase activity in distal nephron: Stimulation by potassium depletion

Am J Physiol Renal Physiol

Ouabain-insensitive K-adenosine triphosphatase in distal nephron segments of the rabbit

J Clin Invest

Case Reports
ATP6B1 gene mutations associated with distal renal tubular acidosis and deafness in a child★

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

Selectively amplified expression of an isoform of the vacuolar H⁺ ATPase 56-kilodalton subunit in renal intercalated cells

An H⁺ ATPase in opposite plasma membrane domains in kidney epithelial cell subpopulations