Genotype/Phenotype Analysis in 67 Chinese Patients with Gitelman's Syndrome

Liu, Ting; Wang, Cui; Lu, Jingru; Zhao, Xiangzhong; Lang, Yanhua; Shao, Leping

doi:10.1159/000448694

Cited by 36 publications

(36 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, for some patients with a poor effect of potassium supplementation, we can try to increase the dosage of magnesium supplementation. Previous studies reported that spironolactone might be helpful for hypokalemia to some degree, and spironolactone combined with potassium supplements tended to be more effective [ 22 , 23 ], but we did not find an advantage of spironolactone treatment. During follow-up, one GS patient developed IFG and two patients presented proteinuria.…”

Section: Discussioncontrasting

confidence: 92%

“…We found four recurrent mutants in SLC12A3, which would provide significant information for the screening and genetic counseling of GS. Consistent with our study, Shao, Tseng and Liu et al also considered the missense mutations T60M and D486 N as highly frequent mutations in the Chinese population [ 8 , 23 , 29 ]. Although GS is inherited in an autosomal recessive manner, up to 30% of patients have simple heterozygous mutations [ 30 ].…”

Section: Discussionsupporting

confidence: 91%

“…There are several possible reasons why we did not discover any mutations in the second allele: (a) existing sequencing methods can only screen exons and their intron–exon boundaries, which are incapable of finding mutations located in gene-regulating sequences such as the 5′-untranslated region and 3′-untranslated region, promoter and enhancer segments, or some harboring deep intronic mutations [ 16 ]; (b) it is difficult to identify gene sequence rearrangements involving one or more exons based on single exon analysis [ 31 ]; (c) the normal NCC protein is inactivated in some way by mutant proteins, such as kinases 1 and 4 with no lysine [ 32 , 33 ]; and (d) epigenetic modifications and/or silent polymorphisms could influence the expression of the NCC [ 34 ]. In addition, one (approximately 5.8%) patient was determined to carry three SLC12A3 mutations, which was in line with other published reports [ 23 ].…”

Section: Discussionsupporting

confidence: 90%

See 2 more Smart Citations

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Zhong

Hui

Jia

et al. 2018

J Endocrinol Invest

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Zhong

Hui

Jia

et al. 2018

J Endocrinol Invest

View full text Add to dashboard Cite

show abstract

“…We believe this work would facilitate a better understanding of the pathogenesis for GS. In addition, patients with multiple mutations (≥3 mutations) observed in our study (10.9%) were also reported by other studies with a proportion of 6.0% to 12.0% ( 4,33,34 ). Since part of the mutations are classified as “uncertain significance” based on current data without functional studies, more in vitro or in vivo functional studies are needed to help provide evidence and disclose the genetic disorder for the multiple mutations.…”

Section: Discussionsupporting

confidence: 90%

Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort

et al. 2020

View full text Add to dashboard Cite

Aim Gitelman syndrome (GS) is a rare inherited salt‐losing renal tubulopathy. Data on clinical features and the pregnancy outcome for female GS patients in a large cohort are lacking. The study was aimed to explore the phenotype and pregnant issue for female GS patients. Methods GS cases from the National Rare Diseases Registry System of China (NRSC) were collected, and detailed clinical, laboratory and genetic data were analysed. Articles on pregnancy in GS were also systemically reviewed. Results A total of 101 GS patients were included; among them, 42.6% were female and 79.2% showed hypomagnesaemia. A lower proportion of female patients presented before 18 years of age, with less frequently reported polyuria, higher serum potassium and less urine sodium and chloride excretions. There was no gender difference in the sodium‐chloride cotransporter (NCC) dysfunction evaluated by hydrochlorothiazide test. Twelve of the 43 female GS patients delivered after disease symptom onset, and their pregnancies were generally uneventful. As a group, pregnant GS patients had lower potassium levels in the first‐trimester (P = .002) requiring higher potassium supplementation. After delivery, serum potassium (P = .02) and magnesium (P = .03) increased significantly. Both caesarean section and vaginal delivery were safe. Conclusion Female GS patients may have a less severe phenotype with generally favourable outcomes of pregnancy. Intensive monitoring and increased potassium supplementation are necessary during pregnancy, especially in the first‐trimester.

show abstract

“…No other signi cant difference was detected in the clinical parameters evaluated in this study. However, some authors have already demonstrated that the hypokalemia is more di cult to be corrected in BS type 3 than BS type 1 or type 2 [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Genetic spectrum of Brazilian suspected Bartter Syndrome Patients

Achl¹,

JCdOA²,

Fonseca³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background This paper’s goal is to show the genetic study results of suspected Bartter syndrome (BS) patients followed in a pediatric nephrology reference center in Sao Paulo/Brazil, verify a possible genotype-phenotype correlation and compare the genetic results with those from other regions of the globe. Results This descriptive study included 22 patients (21 families) with clinical diagnosis of BS. Pathogenic variants in BS-related genes were detected in 19/22 patients. No BS-related genes were detected in three patients (one case of Congenital Chloride Diarrhea and two siblings with clinical Antenal BS that, in fact, had Gitelman Syndrome). We observed that 16/19 BS-confirmed patients had CLCNKB mutations (BS type 3) with a large phenotypical diversity. Among them, the deletion of the entire gene (del 1–20) was the most frequent variant detected. Interestingly, we observed that patients with homozygous or heterozygous del 1–20 presented earlier manifestations than patients with other CLCNKB mutations. They presented no other clinical significant difference. Conclusion This study demonstrates the importance of an appropriate investigation of clinically suspected BS patients to rule out pseudo-BS. This data also confirms the difficult to differentiate these patients based just on clinical findings, similar to what has been reported in other studies. There were patients with clinical Antenatal BS in whom the genetic analysis confirmed the final diagnosis of GS or BS type 3. Among BS cases, BS type 3 was the most frequent in this Brazilian cohort and del 1–20 was the most frequently variant detected. In addition, BS type 3 patients with homozygous or heterozygous del 1–20 had earlier manifestations than patients with other CLCNKB mutations. Brazilian community has a particular characteristic miscegenation as well as different origins such as Europeans, Africans and Asians and comparing our results with those from other regions we can suppose the genetic background of this Brazilian cohort is related to African and Portuguese inheritance, probably originated in the early period of immigration (colonization and slavery period). Limitations: low number of patients from a single center. However, as a rare disease all data can contribute to the improvement for diagnosis and treatment.

show abstract

Genotype/Phenotype Analysis in 67 Chinese Patients with Gitelman's Syndrome

Cited by 36 publications

References 36 publications

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort

Genetic spectrum of Brazilian suspected Bartter Syndrome Patients

Contact Info

Product

Resources

About