Identification of two novel mutations in <i><scp>SLC</scp>12A3</i> gene in two Chinese pedigrees with Gitelman syndrome and review of literature

Li, Congcong; Zhou, Xinjie; Han, Wenxia; Jiang, Xiuyun; Liu, Jia; Li, Fang; Wang, Hai; Guan, Qingbo; Gao, Ling; Zhao, Jiajun; Xu, Jin; Xu, Chao

doi:10.1111/cen.12820

Cited by 17 publications

(21 citation statements)

References 35 publications

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“…T163 M is located in the first transmembrane domain [7]. We speculate the mechanism of T163 M as impairing insertion of an otherwise functional protein into plasma membrane according to other mutation of the same domain [20]. Further animal and molecular biology experiments are needed to verify this speculation.…”

Section: Discussionmentioning

confidence: 91%

“…How these mutations cause GS? At least five potential mechanisms were reported [19,20]: impairing protein synthesis, impairing protein processing, impairing insertion of an otherwise functional protein into the plasma membrane, impairing the functional properties of the cotransporter and accelerating protein removal or degradation. Until now, only 40 mutations were identified by functional experiments, T163 M in this pedigree was not included.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review

Lü

Zhang

Cui

et al. 2015

J Endocrinol Invest

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review

Lü

Zhang

Cui

et al. 2015

J Endocrinol Invest

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“…23 Mutations in the same domain may play a similar role in NCCT impairment and we speculate that the functional mechanism of the M279R mutation might mimic other mutations in the same domain. 22,23 Further animal and molecular biology experiments are needed to verify this speculation. In this current case, no other cause of hypokalaemia was identified except the definite M279R mutation.…”

Section: Discussionmentioning

confidence: 99%

“…25 Missense mutations are the most common, but ‘hotspot’ mutations have not been identified. 22 Compound heterozygous mutations are more common than homozygous mutations. 25 Most patients have compound heterozygous mutations with two different mutations in two alleles.…”

Section: Discussionmentioning

confidence: 99%

Consideration of the diagnosis of hypertension accompanied with hypokalaemia: monism or dualism?

Dong

Wan³

et al. 2018

J Int Med Res

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This case report describes a 53-year-old male patient with persistent hypertension and hypokalaemia. Laboratory tests showed that the patient had hypokalaemia, hypocalcaemia and reduced urine calcium/creatinine. Levels of aldosterone and renin activity were increased significantly. Serum levels of adrenocorticotropic hormone, plasma total cortisol level, 24-h urinary-free cortisol, catecholamines, thyroid stimulating hormone and free tetraiodothyronine were normal. A novel single heterozygous mutation (c.836T> G [E6]) was found after full sequencing of the solute carrier family 12 member 3 (SLC12A3) gene exons. The patient was diagnosed as having primary hypertension with Gitelman syndrome (GS). These findings triggered the careful consideration of whether a monistic or dualist approach to the diagnosis of this patient was the most appropriate. Monism may not always be the most appropriate approach for the diagnosis of coexistent hypertension and hypokalaemia. Consideration should be given to the possibility of the independent existence of distinct diseases (i.e. dualism) when secondary hypertension cannot be confirmed by conventional examinations and when a genetic diagnosis is crucial. As a common cause of hypokalaemia with a high level of clinical phenotypic variation, GS does not conform to the usual diagnostic criteria. It should also be noted that single heterozygous SLC12A3 gene mutations can cause disease symptoms and other genetic mutations might be involved in the pathogenesis of GS.

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“…This could be explained by the fact that GS is more severe in patients with two mutant alleles than those with only one mutated allele (21). Indeed, patients with homozygous mutations are reported to have more severe symptoms than those with heterozygous mutations, as well as an increased risk of developing chronic kidney damage and diabetes mellitus (22).…”

Section: Discussionmentioning

confidence: 99%

A novel homozygous mutation in the solute carrier family 12 member 3 gene in a Chinese family with Gitelman syndrome

Zhang

Chen

et al. 2016

Braz J Med Biol Res

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Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. We report the genetic characteristics of one suspicious Chinese GS pedigree by gene sequencing. Complete sequencing analysis of the SLC12A3 gene revealed that both the proband and his elder sister had a novel homozygous SLC12A3 mutation: c.2099T>C and p.Leu700Pro. Moreover, the SLC12A3 genes of his mother and daughter encoded the same mutated heterozygote. It was noted that in this pedigree, only the proband complained about recurrent episodes of bilateral lower limb weakness over 8 years, while his elder sister, mother and daughter did not present symptoms. The inconsistent clinical features of this pedigree implied that besides diverse phenotypes possibly originated from the same genotype, gender difference may also dominate the variant GS phenotypes. Further genetic and proteomic research are needed to investigate the precise mechanisms of GS, including the study of specific ethnicities.

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Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees with Gitelman syndrome and review of literature

Abstract: Our findings strongly suggested that the two novel mutations in the SLC12A3 gene are the causative agents of GS, which may provide further insights into the function of this gene and help clinicians better understand this disorder.

Cited by 17 publications

References 35 publications

A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review

A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review

Consideration of the diagnosis of hypertension accompanied with hypokalaemia: monism or dualism?

A novel homozygous mutation in the solute carrier family 12 member 3 gene in a Chinese family with Gitelman syndrome

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