Journal article
Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12
Human genetics, Vol.129(4), pp.397-405
2011
DOI: 10.1007/s00439-010-0930-4
PMID: 21184099
Abstract
Genetic disorders of excessive salt loss from sweat glands have been observed in pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the transmembrane conductance regulator (CFTR), respectively. We identified a novel autosomal recessive form of isolated salt wasting in sweat, which leads to severe infantile hyponatremic dehydration. Three affected individuals from a small Bedouin clan presented with failure to thrive, hyponatremic dehydration and hyperkalemia with isolated sweat salt wasting. Using positional cloning, we identified the association of a Glu143Lys mutation in carbonic anhydrase 12 (CA12) with the disease. Carbonic anhydrase is a zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide to form a bicarbonate anion and a proton. Glu143 in CA12 is essential for zinc coordination in this metalloenzyme and lowering of the protein-metal affinity reduces its catalytic activity. This is the first presentation of an isolated loss of salt from sweat gland mimicking PHA, associated with a mutation in the CA12 gene not previously implicated in human disorders. Our data demonstrate the importance of bicarbonate anion and proton production on salt concentration in sweat and its significance for sodium homeostasis.
Details
- Title: Subtitle
- Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12
- Creators
- Emad MUHAMMAD - Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelNeta LEVENTHAL - Pediatric Endocrinology and Metabolism Unit, Soroka Medical Center, Beer Sheva 84101, IsraelTal NAGAR - National Institute of Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelJohn C BECK - Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, University of Iowa, Iowa City IA 52242, United StatesVal C SHEFFIELD - Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, University of Iowa, Iowa City IA 52242, United StatesEli HERSHKOVITZ - Pediatric Endocrinology and Metabolism Unit, Soroka Medical Center, Beer Sheva 84101, IsraelRuti PARVARI - Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelGalit PARVARI - Department of Organic and Inorganic Chemistry, Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, IsraelAaron HANUKOGLU - Division of Pediatric Endocrinology, E Wolfson Medical Center, Holon 58100, IsraelIsrael HANUKOGLU - Department of Molecular Biology, Ariel University Center, Ariel 40700, IsraelVered CHALIFA-CASPI - National Institute of Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelYael FEINSTEIN - Pediatric Endocrinology and Metabolism Unit, Soroka Medical Center, Beer Sheva 84101, IsraelJenny WEINBRAND - Pediatric Endocrinology and Metabolism Unit, Soroka Medical Center, Beer Sheva 84101, IsraelHarel JACOBY - Pediatric Endocrinology and Metabolism Unit, Soroka Medical Center, Beer Sheva 84101, IsraelEsther MANOR - Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.129(4), pp.397-405
- Publisher
- Springer; Heidelberg
- DOI
- 10.1007/s00439-010-0930-4
- PMID
- 21184099
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Language
- English
- Date published
- 2011
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065482002771
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