Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12

Muhammad, Emad; Leventhal, Neta; Parvari, Galit; Hanukoglu, Aaron; Hanukoglu, Israel; Chalifa‐Caspi, Vered; Feinstein, Yael; Weinbrand, Jenny; Jacoby, Harel; Manor, Esther; Nagar, Tal; Beck, John C.; Sheffield, Val C.; Hershkovitz, Eli; Parvari, Ruti

doi:10.1007/s00439-010-0930-4

Cited by 36 publications

(35 citation statements)

References 42 publications

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“…In accordance with this Astrosclerin 1 was reported to be catalytically inactive, however recombinant Astrosclerin 2 could not be generated [7]. Such mutations in the active site of α-CA are likely to cause a weakening or elimination of zinc-binding capacity, and therefore of catalytic function [87].…”

Section: Conserved Domains In α-Cas Involved In the Metazoan Biocalcimentioning

confidence: 59%

The evolution of metazoan α-carbonic anhydrases and their roles in calcium carbonate biomineralization

et al. 2014

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The carbonic anhydrase (CA; EC 4.2.1.1) superfamily is a class of ubiquitous metallo-enzymes that catalyse the reversible hydration of carbon dioxide. The α-CA family, present in all metazoan clades, is a key enzyme involved in a wide range of physiological functions including pH regulation, respiration, photosynthesis, and biocalcification. This paper reviews the evolution of the α-CA family, with an emphasis on metazoan α-CA members involved in biocalcification. Phylogenetic analyses reveal a complex evolutionary history of α-CAs, and suggest α-CA was independently co-opted into a variety of skeleton forming roles (e.g. as a provider of HCO 3 − ions, a structural protein, a nucleation activator, etc.) in multiple metazoan lineages. This evolutionary history is most likely the result of multiple gene duplications coupled with the insertion of repetitive or non-repetitive low-complexity domains (RLCDs/LCDs). These domains, of largely unknown function, appear to be lineage-specific, and provide further support for the hypothesis of independent recruitment of α-CAs to diverse metazoan biocalcification processes. An analysis of α-CA sequences associated with biocalcification processes indicates that the domains involved in the activity and conformation of the active site are extremely conserved among metazoans.

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Section: Conserved Domains In α-Cas Involved In the Metazoan Biocalcimentioning

confidence: 59%

The evolution of metazoan α-carbonic anhydrases and their roles in calcium carbonate biomineralization

et al. 2014

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“…MGAT5 and MGAT5B are both known to be involved in the biosynthesis of N-glycans [62, 68], and both genes have been implicated as positional candidates for large-effect DMI QTL in Angus and Hereford (Table 4). Moreover, the positional candidate genes RAB12 (24_41 Mb), NEGR1 (3_73 Mb), RAB37 (19_57 Mb), and CA12 / LACTB (10_47 Mb) have also been associated with autophagy related to cellular nutrient sensing in mice [69], feed intake and/or obesity traits in humans and rats [70–72], insulin release in mice [73], hyponatremia in humans with loss of appetite and poor weight gain [74], and adiposity in humans [75] (Table 4). Importantly, the biochemical roles and pathway relationships between insulin and glucagon with respect to food intake, satiety, and body weight have been reported and reviewed, with both insulin and glucagon normally acting to reduce meal size [76, 77].…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle

et al. 2017

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BackgroundSingle nucleotide polymorphism (SNP) arrays for domestic cattle have catalyzed the identification of genetic markers associated with complex traits for inclusion in modern breeding and selection programs. Using actual and imputed Illumina 778K genotypes for 3887 U.S. beef cattle from 3 populations (Angus, Hereford, SimAngus), we performed genome-wide association analyses for feed efficiency and growth traits including average daily gain (ADG), dry matter intake (DMI), mid-test metabolic weight (MMWT), and residual feed intake (RFI), with marker-based heritability estimates produced for all traits and populations.ResultsModerate and/or large-effect QTL were detected for all traits in all populations, as jointly defined by the estimated proportion of variance explained (PVE) by marker effects (PVE ≥ 1.0%) and a nominal P-value threshold (P ≤ 5e-05). Lead SNPs with PVE ≥ 2.0% were considered putative evidence of large-effect QTL (n = 52), whereas those with PVE ≥ 1.0% but < 2.0% were considered putative evidence for moderate-effect QTL (n = 35). Identical or proximal lead SNPs associated with ADG, DMI, MMWT, and RFI collectively supported the potential for either pleiotropic QTL, or independent but proximal causal mutations for multiple traits within and between the analyzed populations. Marker-based heritability estimates for all investigated traits ranged from 0.18 to 0.60 using 778K genotypes, or from 0.17 to 0.57 using 50K genotypes (reduced from Illumina 778K HD to Illumina Bovine SNP50). An investigation to determine if QTL detected by 778K analysis could also be detected using 50K genotypes produced variable results, suggesting that 50K analyses were generally insufficient for QTL detection in these populations, and that relevant breeding or selection programs should be based on higher density analyses (imputed or directly ascertained).ConclusionsFourteen moderate to large-effect QTL regions which ranged from being physically proximal (lead SNPs ≤ 3Mb) to fully overlapping for RFI, DMI, ADG, and MMWT were detected within and between populations, and included evidence for pleiotropy, proximal but independent causal mutations, and multi-breed QTL. Bovine positional candidate genes for these traits were functionally conserved across vertebrate species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3754-y) contains supplementary material, which is available to authorized users.

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“…We have recently identified subjects of Bedouin families from two distinct clans with a mutation in CA XII (OMIM: 143860) leading to a unique clinical and biochemical entity of hyponatremia due to excessive salt loss from sweat glands [5,6]. The autosomal recessive disorder delineated in our studies constitutes the first demonstration that mutant CA XII is related to salt wasting in sweat.…”

Section: Introductionmentioning

confidence: 86%

“…In our homozygous patients the amino acid glutamate at position 143 in CA XII was replaced by lysine [6]. The mutant protein demonstrated reduced CA XII activity compared to the wild-type CA XII [5].…”

Section: Introductionmentioning

confidence: 99%

Natural History and Clinical Manifestations of Hyponatremia and Hyperchlorhidrosis due to Carbonic Anhydrase XII Deficiency

Feinstein

Yerushalmi²,

Loewenthal³

et al. 2014

Horm Res Paediatr

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Introduction: We identified patients of Bedouin origin with a mutation in carbonic anhydrase XII (CA XII) leading to hyponatremia due to excessive salt loss via sweat. Methods: The medical records of patients were reviewed for clinical and laboratory data. Results: A total of 11 subjects were identified; 7 symptomatic patients presented with hyponatremic dehydration in infancy. Screening of the entire kindred identified 4 asymptomatic individuals with elevated sweat chloride. All symptomatic patients had failure to thrive and moderate-severe hyponatremia (106-124 mmol·l^-1); 6 had hypochloremia (79-94 mmol·l^-1). All asymptomatic subjects had normal or near-normal serum sodium and chloride concentrations. Both symptomatic and asymptomatic subjects had normal renal functions and normal cortisol response on low-dose ACTH test. All symptomatic patients were treated by dietary salt, which prevents episodes of hyponatremic dehydration and promotes growth. At follow-up, the chief complaints remained heat intolerance, accumulation of salt precipitates on the face and hyperhidrosis. No evidence for chronic renal, respiratory, gastrointestinal or fertility abnormalities was found. Conclusion: Recognizing this newly described entity and differentiating it from cystic fibrosis and pseudohypoaldosteronism are important. Patients with CA XII mutations should be followed even after early childhood, especially in hot temperatures and intense physical activity.

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Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12

Cited by 36 publications

References 42 publications

The evolution of metazoan α-carbonic anhydrases and their roles in calcium carbonate biomineralization

The evolution of metazoan α-carbonic anhydrases and their roles in calcium carbonate biomineralization

Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle

Natural History and Clinical Manifestations of Hyponatremia and Hyperchlorhidrosis due to Carbonic Anhydrase XII Deficiency

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