<i>ATP6V1B1</i>mutations in distal renal tubular acidosis and sensorineural hearing loss: clinical and genetic spectrum of five families

Uzak, Asli Subasioglu; Çakar, Nilgün; Çomak, Elif; Yalçınkaya, Fatoş; Tekin, Mustafa

doi:10.3109/0886022x.2013.824362

Cited by 11 publications

(7 citation statements)

References 12 publications

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“…Hair cells in human inner ear convert sound vibrations into electrical signals to provide the basis for hearing. Some patients with distal renal tubular acidosis that have mutations in ATP6V1B1 or ATP6V0A4 , which encode the V-ATPase V 1 B1 and V o a4 subunits, respectively, develop sensorineural hearing loss, which is typically caused by damage to the sensory hair cells and/or nerve fibers of the inner ear ( Karet et al, 1999 ; Stover et al, 2002 ; Vargas-Poussou et al, 2006 ; Subasioglu Uzak et al, 2013 ). How these mutations impact hearing is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Loss of vacuolar-type H+-ATPase induces caspase-independent necrosis-like death of hair cells in zebrafish neuromasts

Santra

Amack

2021

Disease Models &Amp; Mechanisms

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The vacuolar type H+-ATPase (V-ATPase) is a ubiquitous membrane-bound, multi-subunit proton pump that regulates pH of cellular compartments. V-ATPase activity is known to modulate several cellular processes, but cell type-specific V-ATPase functions remain poorly understood. Patients with mutations in specific V-ATPase subunits can develop sensorineural deafness, but underlying mechanisms are unclear. Here, we show that V-ATPase mutations disrupt formation of zebrafish neuromasts, which serve as a model system to investigate the underpinnings of hearing loss. Neuromasts consist of support cells surrounding mechanosensory hair cells that function similarly to hair cells in the mammalian inner ear. In V-ATPase mutant zebrafish embryos, neuromasts are small, malformed, and contain pyknotic nuclei that denote dying cells. Using molecular markers and live imaging, we find that loss of V-ATPase induces hair cells, but not neighboring support cells, to undergo caspase-independent necrosis-like cell death. This is the first demonstration that loss of V-ATPase can lead to necrosis-like cell death in a specific cell type in vivo. Mechanistically, loss of V-ATPase reduces mitochondrial membrane potential in hair cells, which has previously been associated with necrotic cell death. Modulating the mitochondrial permeability transition pore, which regulates mitochondrial membrane potential, improves hair cell survival. These results have implications for understanding causes of sensorineural deafness, and more broadly, reveal functions for V-ATPase in regulating mitochondrial function and promoting survival of a specific cell type in vivo.

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Section: Introductionmentioning

confidence: 99%

Loss of vacuolar-type H+-ATPase induces caspase-independent necrosis-like death of hair cells in zebrafish neuromasts

Santra

Amack

2021

Disease Models &Amp; Mechanisms

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“…In addition, the high prevalence of consanguinity within North African populations (El Bouchikhi et al 2020;Mete et al 2020) may be the driving force for the spread of ATP6V1B1 variants in these populations. However, the association of ATP6V1B1 variants with HI is not exclusive to North Africa, there were reports from other parts of the world including the USA (Subasioglu Uzak et al 2013), and Japan (Yashima et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Hearing loss in Africa: current genetic profile

et al. 2021

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Hearing impairment (HI) is highly heterogeneous with over 123 associated genes reported to date, mostly from studies among Europeans and Asians. Here, we performed a systematic review of literature on the genetic profile of HI in Africa. The study protocol was registered on PROSPERO, International Prospective Register of Systematic Reviews with the registration number “CRD42021240852”. Literature search was conducted on PubMed, Scopus, Africa-Wide Information, and Web of Science databases. A total of 89 full-text records was selected and retrieved for data extraction and analyses. We found reports from only 17/54 (31.5%) African countries. The majority (61/89; 68.5%) of articles were from North Africa, with few reports found from sub-Saharan Africa. The most common method used in these publications was targeted gene sequencing (n = 66/111; 59.5%), and only 13.5% (n = 15/111) used whole-exome sequencing. More than half of the studies were performed in families segregating HI (n = 51/89). GJB2 was the most investigated gene, with GJB2: p.(R143W) founder variant only reported in Ghana, while GJB2: c.35delG was common in North African countries. Variants in MYO15A were the second frequently reported in both North and Central Africa, followed by ATP6V1B1 only reported from North Africa. Usher syndrome was the main syndromic HI molecularly investigated, with variants in five genes reported: USH2A, USH1G, USH1C, MYO7A, and PCDH15. MYO7A: p.(P1780S) founder variant was reported as the common Usher syndrome variant among Black South Africans. This review provides the most comprehensive data on HI gene variants in the largely under-investigated African populations. Future exomes studies particularly in multiplex families will likely provide opportunities for the discovery of the next sets of novel HI genes, and well as unreported variants in known genes to further our understanding of HI pathobiology, globally.

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“…Mutations in the ATP6V1B1 gene encoding the B1 subunit of vacuolar H-ATPase result in autosomal recessive dRTA associated with sensorineural hearing loss [ 31 ]. None of the 3 patients reported here reported hearing alterations.…”

Section: Discussionmentioning

confidence: 99%

Distal Renal Tubular Acidosis Associated with Autoimmune Diseases: Reports of 3 Cases and Review of Mechanisms

et al. 2021

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Case series Patients: Female, 29-year-old • Female, 67-year-old • Female, 30-year-old Final Diagnosis: Distal renal tubular acidosis (dRTA) Symptoms: Hypokalemia • metabolic acidosis Medication: — Clinical Procedure: Diagnosis Specialty: Nephrology • Rheumatology Objective: Unusual clinical course Background: Distal renal tubular acidosis (dRTA) is a defect in the urinary acidification process that limits the elimination of protons [H+] by alpha intercalated cells in the collecting tubules, with consequent metabolic acidosis with a normal plasma anion gap. The relationship between this tubulopathy and immune-mediated diseases like Sjögren syndrome, rheumatoid arthritis, autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus, and thyroiditis is well known. Further, the pathophysiological mechanisms are diverse, but, unfortunately, many are not yet fully understood. We report 3 cases of dRTA in patients with different autoimmune diseases and review the pathophysiological mechanisms already described. Case Reports: The first case involved a 29-year-old woman with autoimmune hepatitis. She had metabolic acidosis with persistent hypokalemia, and a kidney stone was also identified. The second case involved a 67-year-old woman diagnosed with rheumatoid arthritis. She had metabolic acidosis with hypokalemia. The third case involved a 30-year-old woman with Sjögren syndrome and persistent metabolic acidosis. In addition to the presence of metabolic acidosis with a normal plasma anion gap, all 3 patients exhibited urine with a supraphysiologic pH (above 5.3). Conclusions: Autoimmune diseases may be associated with deficits in urinary acidification with consequent metabolic acidosis and, therefore, systemic repercussions. This association must be remembered and researched because correct diagnosis and treatment will serve to reduce complications.

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ATP6V1B1mutations in distal renal tubular acidosis and sensorineural hearing loss: clinical and genetic spectrum of five families

Cited by 11 publications

References 12 publications

Loss of vacuolar-type H+-ATPase induces caspase-independent necrosis-like death of hair cells in zebrafish neuromasts

Loss of vacuolar-type H+-ATPase induces caspase-independent necrosis-like death of hair cells in zebrafish neuromasts

Hearing loss in Africa: current genetic profile

Distal Renal Tubular Acidosis Associated with Autoimmune Diseases: Reports of 3 Cases and Review of Mechanisms

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