ArticleHuman molecular genetics2016
Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Human Nasal and Bronchial Epithelium in Cystic Fibrosis: Differences in Expression of Airway pH Regulatory Proteins.Pediatric pulmonology · 2026Article
- Characterizing individuals with elevated sweat chloride results in the absence of CFTR variants.Orphanet journal of rare diseases · 2025Article
- pH Homeodynamics and Male Fertility: A Coordinated Regulation of Acid-Based Balance during Sperm Journey to Fertilization.Biomolecules · 2024Review
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- Review
- Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Case Report: NovelFrontiers in pediatrics · 2022Article
- Large pH oscillations promote host defense against human airways infection.The Journal of experimental medicine · 2021Article
- Airway Surface Liquid pH Regulation in Airway Epithelium Current Understandings and Gaps in Knowledge.International journal of molecular sciences · 2021Review
- TNFα and IL-17 alkalinize airway surface liquid through CFTR and pendrin.American journal of physiology. Cell physiology · 2020Article
- Carbonic anhydrases as disease markers.Expert opinion on therapeutic patents · 2019Review
- Integrated Transcriptomic and Proteomic Analysis of Human Eccrine Sweat Glands Identifies Missing and Novel Proteins.Molecular & cellular proteomics : MCP · 2019Article
- Carbonic Anhydrases: Role in pH Control and Cancer.Metabolites · 2018Review
- Nominal carbonic anhydrase activity minimizes airway-surface liquid pH changes during breathing.Physiological reports · 2018Article
- Review
- Article
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.908-1 G>A in a splice acceptor and a novel frameshift insertion c.859_860insACCT. In an unrelated consanguineous Omani family, two children with elevated sweat chloride, infantile FTT, and recurrent hyponatremia were homozygous for a novel missense variant (p.His121Gln). Deleterious CFTR variants were absent in both pedigrees. CA XII protein was localized apically in human bronchiolar epithelia and basolaterally in the reabsorptive duct of human sweat glands. Respiratory epithelial cell RNA from the adult proband revealed only aberrant CA12 transcripts and in vitro analysis showed greatly reduced CA XII protein. Studies of ion transport across respiratory epithelial cells in vivo and in culture revealed intact CFTR-mediated chloride transport in the adult proband. CA XII protein bearing either p.His121Gln or a previously identified p.Glu143Lys missense variant localized to the basolateral membranes of polarized Madin-Darby canine kidney (MDCK) cells, but enzyme activity was severely diminished when assayed at physiologic concentrations of extracellular chloride. Our findings indicate that loss of CA XII function should be considered in individuals without CFTR mutations who exhibit CF-like features in the sweat gland and lung.
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Registered trials
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