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

Lü, Qing; Zhang, Y.; Cui, Song; An, Zhenmei; Wei, Shanghai; Huang, Jingwen; Huang, Lijuan; Tang, Lei; Tong, Nanwei

doi:10.1007/s40618-015-0371-y

Cited by 21 publications

(12 citation statements)

References 29 publications

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“…To date, 453 mutations have been deposited in the Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ ). Interestingly, the phenotype of GS patients is highly heterogeneous [ 7 ]. Some researchers have analyzed the clinical and genetic characteristics in unrelated patients with GS.…”

Section: Introductionmentioning

confidence: 99%

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Zhong

Hui

Jia

et al. 2018

J Endocrinol Invest

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Context Gitelman syndrome (GS) is clinically heterogeneous. The genotype and phenotype correlation has not been well established. Though the long-term prognosis is considered to be favorable, hypokalemia is difficult to cure. Objective To analyze the clinical and genetic characteristics and treatment of all members of 13 GS pedigrees. Methods Thirteen pedigrees (86 members, 17 GS patients) were enrolled. Symptoms and management, laboratory findings, and genotype–phenotype associations among all the members were analyzed. Results The average ages at onset and diagnosis were 27.6 ± 10.2 years and 37.9 ± 11.6 years, respectively. Males were an average of 10 years younger and exhibited more profound hypokalemia than females. Eighteen mutations were detected. Two novel mutations (p.W939X, p.G212S) were predicted to be pathogenic by bioinformatic analysis. GS patients exhibited the lowest blood pressure, serum K + , Mg 2+ , and 24-h urinary Ca 2+ levels. Although blood pressure, serum K + and Mg 2+ levels were normal in heterozygous carriers, 24-h urinary Na + excretion was significantly increased. During follow-up, only 41.2% of patients reached a normal serum K + level. Over 80% of patients achieved a normal Mg 2+ level. Patients were taking 2–3 medications at higher doses than usual prescription to stabilize their K + levels. Six patients were taking spironolactone simultaneously, but no significant elevation in the serum K + level was observed. Conclusion The phenotypic variability of GS and therapeutic strategies deserve further research to improve GS diagnosis and prognosis. Even heterozygous carriers exhibited increased 24-h Na + urine excretion, which may make them more susceptible to diuretic-induced hypokalemia. Electronic supplementary material The online version of this article (10.1007/s40618-018-0966-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Zhong

Hui

Jia

et al. 2018

J Endocrinol Invest

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“…However, several previous studies have shown that female GS patients/carriers are much less severely affected than male GS subjects (6,7,23). As we have previously reported on a pedigree carrying a novel SLC12A3 gene homozygous mutation of GS in three patients with the homozygous mutation, the male proband also had more severe clinical symptoms and laboratory findings, and a poorer prognosis than the other two female relatives (14). These evidences suggest that gender may play a crucial role in phenotypic diversity.…”

Section: Discussionmentioning

confidence: 51%

“…Gene amplification was performed by polymerase chain reaction (PCR) of 3 ng/mL DNA samples with the Ion AmpliSeq™ Library Kit (Life Technology, USA). PCR was conducted using SLC12A3 primers (listed in Supplementary Table S1) on a GeneAmp 9700 PCR system (ABI) under the following conditions (8,12, 14): 5-min predenaturation and 30-s denaturation at 95°C, annealing at 57-64°C, and 90-s chain extension at 72°C; the above steps were recycled 30 times. All sample densities were of 3 ng/mL.…”

Section: Methodsmentioning

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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“…To date, 488 mutations of the SLC12A3 gene have been discovered in patients with GS (HGMD, professional 2017.1), including missense mutations, shear mutations, nonsense mutations, and frame shift mutations, among which missense mutations are the most commonly described. Moreover, compound heterozygous mutations are more common than homozygous mutations [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome pedigree

Chen¹,

Zhang²,

Lin³

et al. 2018

BMC Med Genet

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Background: Gitelman syndrome (GS) is an autosomal recessive disorder caused by genic mutations of SLC12A3 (Solute carrier family 12 member 3), which encodes the Na-Cl cotransporter (NCC), and presents with characteristic metabolic abnormalities, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this study, we report a case of a GS pedigree, including analysis of GS-associated gene mutations.

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

Cited by 21 publications

References 29 publications

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

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

A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome pedigree

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