Late-Onset Bartter's Syndrome Type II with End-Stage Renal Disease Due to a Novel Mutation in KCNJ1 Gene in an Indian Adult Male - A Case Report.

Mutations in ROMK1 potassium channel gene (KCNJ1) causes antenatal/neonatal Bartter's syndrome type II, which presents with renal salt wasting, hypokalemic metabolic alkalosis, secondary hyperaldosteronism, hypercalciuria, and nephrocalcinosis. We herein describe a case of late-onset Bartter's syndrome type II with progressive renal failure requiring renal replacement therapy secondary to a novel homozygous missense mutation in Exon 2 of KCNJ1 gene (c.500G>A). With this case, we aim to highlight the need for a high index of suspicion and the role of genetic evaluation to diagnose clinically unclassified cases of nephrocalcinosis with renal electrolyte abnormalities more so in late and atypical presentations.

Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.

BACKGROUND: In recent years, morbidity and mortality from colorectal cancer have increased. Colorectal adenoma is the main precancerous lesion. Understanding the pathogenesis of colorectal adenoma will help to improve the early diagnosis rate of colorectal cancer. METHODS: In this case-control study, we focused on three single nucleotide polymorphisms (SNPs) in genes SLC8A1 (rs4952490), KCNJ1 (rs2855798), and SLC12A1 (rs1531916). We analyzed 207 colorectal adenoma patients (112 high-risk cases and 95 low-risk cases) and 212 control subjects by Sanger sequencing. A food frequency questionnaire (FFQ) was used to survey demographic characteristics and dietary nutrition. RESULTS: In the overall analysis, the results suggested that the AA+AG and AG genotype carriers of rs4952490 had a 73.1% and 78% lower risk of colorectal adenoma compared to GG genotype carriers, respectively. However rs2855798 and rs1531916 were not associated with the incidence of colorectal adenoma. Additionally, stratified analysis showed that rs4952490 AA+AG and AG genotypes had a protective effect against low-risk colorectal adenoma in patients aged ≤ 60 years old who were non-smokers. We also observed that when calcium intake was higher than 616 mg/d and patients carried at least one gene with variant alleles there was a protective effect against low-risk colorectal adenoma. CONCLUSIONS: Interactions between dietary calcium intake and calcium reabsorption genes may affect the occurrence and development of colorectal adenoma.

The effect of high-dietary K+ (HK) on Kir4.1/Kir5.1 and ROMK in the distal convoluted tubule (DCT) is not affected by gender and Cl- content of the diet.

Basolateral potassium channels in the distal convoluted tubule (DCT) are composed of inwardly-rectifying potassium channel 4.1 (Kir4.1) and Kir5.1. Kir4.1 interacts with Kir5.1 to form a 40 pS K+ channel which is the only type K+ channel expressed in the basolateral membrane of the DCT. Moreover, Kir4.1/Kir5.1 heterotetramer plays a key role in determining the expression and activity of thiazide-sensitive Na-Cl cotransport (NCC). In addition to Kir4.1/Kir5.1, Kir1.1 (ROMK) is expressed in the apical membrane of the late DCT (DCT2) and plays a key role in mediating epithelial Na+ channel (ENaC)-dependent K+ excretion. High dietary-K+-intake (HK) stimulates ROMK and inhibits Kir4.1/Kir5.1 in the DCT. Inhibition of Kir4.1/Kir5.1 is essential for HK-induced suppression of NCC whereas the stimulation of ROMK is important for increasing ENaC-dependent K+ excretion during HK. We have now used the patch-clamp-technique to examine whether gender and Cl- content of K+-diet affect HK-induced inhibition of basolateral Kir4.1/Kir5.1 and HK-induced stimulation of ROMK. Single-channel-recording shows that basolateral 40 pS K+ channel (Kir4.1/Kir5.1) activity of the DCT defined by NPo was 1.34 (1% KCl, normal K, NK), 0.95 (5% KCl) and 1.03 (5% K+-citrate) in male mice while it was 1.47, 1.02 and 1.05 in female mice. The whole-cell recording shows that Kir4.1/Kir5.1-mediated-K+ current of the early-DCT (DCT1) was 1,170 pA (NK), 725 pA (5% KCl) and 700 pA (5% K+-citrate) in male mice whereas it was 1,125 pA, 674 pA and 700 pA in female mice. Moreover, K+-currents (IK) reversal potential of DCT (an index of membrane potential) was -63 mV (NK), -49 mV (5% KCl) and -49 mV (5% K-citrate) in the male mice whereas it was -63 mV, -50 mV and -50 mV in female mice. Finally, TPNQ-sensitive whole-cell ROMK-currents in the DCT2 /initial-connecting tubule (CNT) were 910 pA (NK), 1,520 pA (5% KCl) and 1,540 pA (5% K+-citrate) in male mice whereas the ROMK-mediated K+ currents were 1,005 pA, 1,590 pA and 1,570 pA in female mice. We conclude that the effect of HK intake on Kir4.1/Kir5.1 of the DCT and ROMK of DCT2/CNT is similar between male and female mice. Also, Cl- content in HK diets has no effect on HK-induced inhibition of Kir4.1/Kir5.1 of the DCT and HK-induced stimulation of ROMK in DCT2/CNT.

A novel mutation of KCNJ1 identified in an affected child with nephrolithiasis.

Nephrolithiasis is not common in children, but the incidence is gradually increased in these years. Urinary tract malformations, urinary infection, dietary habits, geographic region and genetic factor are involved in the etiology of nephrolithiasis. For the affected child, it is especially important to elucidate the etiology, which may provide an accurate diagnosis, a personalized therapy and effective follow-up strategy. Here to seek the etiology of a ten-year-old boy incidentally found with nephrolithiasis, next generation sequencing (NGS) including a panel with 248 genes involved in hereditary kidney diseases was performed for the boy and identified two mutations of KCNJ1, c.89G > A (p.C30Y) and c.65G > T (p.R22M), and the later was a novel missense mutation originated from his father. The child was confirmed with type II Bartter syndrome (BS) caused by KCNJ1 mutations. Our study suggests that BS may be difficult to get diagnosed at an early stage based on clinical manifestations or biochemical laboratory tests, and NGS is an efficient way to determine the etiology and provide further treatment and guide fertility counseling for the affected family.

Late-Onset Bartter Syndrome Type II Due to a Novel Compound Heterozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review.

Background: Bartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle's loop. BS type II is typically considered as a disorder of infancy and seldom seen in adults. Case Presentation: A 34-year-old woman was admitted with generalized body numbness and hand convulsions, without growth retardation. Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. She was misdiagnosed during the initial diagnosis process and was finally diagnosed with late-onset BS type II via genetic testing through next-generation sequencing combined with Sanger sequencing. A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene from her parents was identified and speculated to be a potential pathogenic gene variation. Conclusion: We report a case of late-onset BS type II with a novel compound heterozygous mutation in KCNJ1. Both variants are novel and have never been reported. Our report will have a significant impact on the diagnosis of BS in other patients without typical clinical presentations and emphasizes the importance of genetic investigation.

Genetic evaluation of paediatric nephrocalcinosis: phenotype-driven genetic panels reveal a rare diagnosis.

Monogenic causes of paediatric nephrocalcinosis are associated with extensive phenotypic variability. We report a 14-year-old male who presented at 8 years of age with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies. Extensive genetic investigation confirmed a molecular diagnosis of Bartter syndrome type II. This is exceptional in both late presentation and the presence of amelogenesis imperfecta, a very rare association of inherited tubulopathies. Details of the nephrocalcinosis gene panel analysed and associated phenotypes are presented to highlight the utility of a phenotype-driven genetic panel in resolving an atypical presentation of nephrocalcinosis, allowing precise diagnosis, tailored therapy and prognostication.

Clinical exome sequencing uncovers an unsuspected diagnosis of Bartter syndrome type 2 in a child with incidentally detected nephrocalcinosis.

Nephrocalcinosis is a characteristic feature of both type 1 and type 2 Bartter syndrome. Bartter syndrome type 2 presents antenatally and very early in life. Late-onset presentation with isolated nephrocalcinosis is extremely rare. We describe an 11-year-old girl with incidentally detected medullary nephrocalcinosis on renal ultrasonography. She was clinically suspected to have primary hyperoxaluria based on high urine oxalate. However, clinical exome sequencing revealed a pathogenic missense variant in the KCNJ1 gene leading to the molecular diagnosis of Bartter syndrome type 2. Both parents were heterozygous carriers of the same variant. Subsequent investigations did reveal a mild Bartter syndrome phenotype with mild metabolic alkalosis, high urine chloride and high renin and aldosterone. Our case illustrates phenotypic heterogeneity of Bartter syndrome type 2 and the usefulness of genetic testing in establishing the correct diagnosis and guiding further management in such cases.

Hypocalcemia as the Initial Presentation of Type 2 Bartter Syndrome: A Family Report.

CONTEXT: Bartter syndrome (BS) is a group of rare autosomal-recessive tubulopathies characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Type 2 BS results from a defect in the renal outer medullary potassium channel encoded by the KCNJ1 gene. Type 2 BS presents with polyhydramnios, intrauterine growth retardation, prematurity, failure to thrive, polyuria, hypercalciuria, and life-threatening episodes of dehydration. Hypocalcemia is a very rare presenting symptom of BS, with only a few published cases reporting it as the initial manifestation of type 2 BS. OBJECTIVE: To describe a child who presented with hypocalcemic seizure at the age of 2.3 years that was first related to vitamin D deficiency and high-phosphate soft drink consumption. METHODS: Whole exome sequencing (WES) was used to evaluate the biochemical abnormalities of the proband. RESULTS: We identified a previously described homozygous missense mutation c.212C>T, p.T71M in the KCNJ1 gene associated with type 2 BS. Six additional family members with the same mutation and diagnosed clinically with BS are also reported, 2 presenting with hypocalcemia associated with vitamin D deficiency. CONCLUSION: This report expands the clinical spectrum associated with KCNJ1 mutations and emphasizes the role of WES in unsolved cases of hypocalcemia when genetic disease is suspected. It also highlights the hazardous effects of phosphate-containing soft drinks on calcium metabolism.

Eight novel KCNJ1 variants and parathyroid hormone overaction or resistance in 5 probands with Bartter syndrome type 2.

PURPOSE: Bartter syndrome type 2 (BS2) is an autosomal recessive renal tubular disorder, which is caused by the mutations in KCNJ1. This study was designed to analyze and describe the genotype and clinical features of five Chinese probands with BS2. METHODS: Identify KCNJ1 gene variants by the next generation sequencing and evaluate their mutation effects according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines. RESULTS: Ten variants including eight novel ones of KCNJ1 gene were found, the most common type was missense variant. The common symptoms and signs from high to low incidence were: polydipsia and polyuria (5/5), one of them (1/5) presented with diabetes insipidus; maternal polyhydramnios and premature delivery (4/5); growth retardation (3/5). Two patients presented with hypochloremic metabolic alkalosis and hypokalemia; whereas the acid-base disturbance was absent in the others. One patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal PTH levels. All patients had nephrocalcinosis and/or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin has significant therapeutic effect on the growth retardation, polydipsia and polyuria and treatment was associated with a decrease in urine calcium excretion, normalization of electrolyte disturbance and PTH parameters. CONCLUSIONS: Ten variants of KCNJ1 gene were identified in five Chinese probands. These patients had atypical BS phenotype lacking evident metabolic alkalosis and/or manifesting with PTH overaction/resistance, which reminds clinicians to carefully differentiate BS2 with other parathyroid disorders. This is the first report of BS2 from Chinese populations.

Severe Polyhydramnios with Consistent Fetal Full Bladder: A Novel Sign of Antenatal Bartter's Disease.

Bartter's disease, an inherited renal tubular disorder is due to a defect in ion transport across the ascending limb of the loop of Henle leading to failure of the ability of kidneys to concentrate urine and hence polyuria. We present three fetuses of mothers with severe polyhydramnios with normal maternal blood sugar profile, routine Toxoplasma, Rubella, Cytomegalovirus, Herpes (TORCH) serology. The ultrasound showed no structural anomaly in the fetus, but consistent overdistended bladder with severe polyhydramnios was observed without any evidence of obstructive uropathy. The biochemical test on amniotic fluid was suggestive of Bartter's disease in case 1 and borderline in case 2, and next-generation sequencing confirmed a mutation of KCNJ1 associated with Bartter's disease Type II in case 1 and a mutation in SLC21A1 in case 2. Amniotic fluid biochemistry was inconclusive in case 3. A consistent full bladder with severe polyhydramnios with onset around 24 to 25 weeks was a novel finding which was observed due to fetal polyuria and can be used as a clue to investigate cases with severe polyhydramnios with no structural anomaly. Antenatal diagnosis will help in the proper management of child and genetic counseling for the next pregnancy.

Global knockout of ROMK potassium channel worsens cardiac ischemia-reperfusion injury but cardiomyocyte-specific knockout does not: Implications for the identity of mitoKATP.

The renal-outer-medullary­potassium (ROMK) channel, mutated in Bartter's syndrome, regulates ion exchange in kidney, but its extra-renal functions remain unknown. Additionally, ROMK was postulated to be the pore-forming subunit of the mitochondrial ATP-sensitive K+ channel (mitoKATP), a mediator of cardioprotection. Using global and cardiomyocyte-specific knockout mice (ROMK-GKO and ROMK-CKO respectively), we characterize the effects of ROMK knockout on mitochondrial ion handling, the response to pharmacological KATP channel modulators, and ischemia/reperfusion (I/R) injury. Mitochondria from ROMK-GKO hearts exhibited a lower threshold for Ca2+-triggered permeability transition pore (mPTP) opening but normal matrix volume changes during oxidative phosphorylation. Isolated perfused ROMK-GKO hearts exhibited impaired functional recovery and increased infarct size when I/R was preceded by an ischemic preconditioning (IPC) protocol. Because ROMK-GKO mice exhibited severe renal defects and cardiac remodeling, we further characterized ROMK-CKO hearts to avoid confounding systemic effects. Mitochondria from ROMK-CKO hearts had unchanged matrix volume responses during oxidative phosphorylation and still swelled upon addition of a mitoKATP opener, but exhibited a lower threshold for mPTP opening, similar to GKO mitochondria. Nevertheless, I/R induced damage was not exacerbated in ROMK-CKO hearts, either ex vivo or in vivo. Lastly, we examined the response of ROMK-CKO hearts to ex vivo I/R injury with or without IPC and found that IPC still protected these hearts, suggesting that cardiomyocyte ROMK does not participate significantly in the cardioprotective pathway elicited by IPC. Collectively, our findings from these novel strains of mice suggest that cardiomyocyte ROMK is not a central mediator of mitoKATP function, although it can affect mPTP activation threshold.

Mutation analysis of KCNJ1 gene and investigation of phenotype in 5 Chinese patients with Bartter syndrome type 2 / 中华肾脏病杂志

Objective@#To identify and analyze the variants of the KCNJ1 gene in five Chinese patients with Bartter syndrome type 2 (BS2), and to describe their clinical features as well as treatment results.@*Methods@#Data and blood samples of five BS2 patients and their relatives confirmed by Qingdao Municipal Hospital from June 2012 to January 2019 were collected. Whole-exome-sequencing (WES) based on the second generation high throughput sequencing was performed to detect variants. The 2015 American College of Medical Genetics and Genomics Standards and Guidelines were applied to analyze the pathogenicity of the variants. The clinical features and laboratory results were retrospectively studied. The response to treatment and follow-up data were reviewed.@*Results@#Ten variants including six novel ones of KCNJ1 gene were identified through WES and verified by Sanger dideoxy sequencing. Missense variants accounted for the highest proportion. The common symptoms and signs of five BS2 patients from high to low incidence were polydipsia and polyuria (5/5), one of them (1/5) presented with diabetes insipidus; maternal polyhydramnios and premature delivery (4/5); growth retardation (3/5). Initially, two patients presented with hypochloremic metabolic alkalosis and hypokalemia, whereas the acid-base disturbance was absent in the others. One patient experienced hyperkalemia. In terms of calcium-phosphorus metabolism, one patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated serum intact PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated serum intact PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal serum intact PTH levels. All patients had nephrocalcinosis or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin helped to correct the growth retardation, halt polydipsia polyuria, decrease the elevated urinary calcium excretion, and normalize electrolyte disturbance as well as PTH parameters in some patients.@*Conclusions@#This investigation identifies ten variants of KCNJ1 gene, including six ones that have not been previously reported, which will enrich the human gene mutation database (HGMD). These patients in our study have atypical BS phenotype, so that careful differentiation from other parathyroid diseases will be required for clinicians.

[The role of estrogen related-receptor γ and ATP-dependent K(+) channel Kcnj1 in renal ischemia-reperfusion injury].

Objective: To investigate the correlation between estrogen related-receptorγ (ERRγ) and ATP-dependent K(+) channel Kcnj1 in renal ischemia-reperfusion injury and its possible role in regulating ischemic preconditioning. Methods: The expression of ERRγ in kidney tissues was detected by immunohistochemistry. The expressions of ERRγ and Kcnj1 in human renal tubular epithelial cells (HK-2) under hypoxia (1% O(2)) were detected by RT-PCR. The ERRγ-deficient heterozygous mice model and the ERRγ-deficient completely mice model were established. The pretreatedischemia-reperfusion model were constructed in wild-type mice, ERRγ-deficient heterozygous mice and ERRγ-deficient completely mice, respectively. Renal injury was observed under a light microscope with PAS staining. ERRγ and Kcnj1 were tested by immunohistochemistry and RT-PCR. Results: ERRγ in mice kidney tissue was mainly expressed in renal tubules, and the expressions of ERRγ and Kcnj1 were decreased 59% and 29.5% respectively after hypoxia in the renal tubular cells (HK-2). In the animal model, the expressions of ERRγ and Kcnj1 were decreased 31.9% and 11% in early ischemic mice kidney tubular cells of wild type. The expressions of ERRγ and Kcnj1 in renal tubular cells were decreased 33.2% and 19.1% after ischemia and reperfusion. When ERRγ were overexpressed in renal tubular cells, ERRγ was increased by 89%, and the expression of Kcnj1 was increased by 72.5%. The expression of Kcnj1 was decreased by 75.7% in ERRγ-deficient completely mice. However, Kcnj1 expression in renal tissue of ERR-γ-deficient mice was stable, but ischemic preconditioning failed to interfere with renal ischemia-reperfusion injury. Conclusion: ERRγ-Kcnj1 is closely related to ischemic preconditioning and protects renal ischemia-reperfusion injury, and may be one of the regulatory factors. To explore the protective effect of the regulating pathway on ischemia reperfusion injury couldprovide a theoretical basis for the development of drug pretreatment.

Late-onset Bartter syndrome type II.

Mutations in the ROMK1 potassium channel gene (KCNJ1) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero, accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

[A clinical and hereditary analysis of novel complex heterozygous KCNJ1 mutation in a Bartter syndrome type â ¡ patient].

Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5). The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria. Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios, polyuria, nephrocalcinosis and hypokalemia, which was alleviated after treatment with celecoxib and vitamin D(3). DNA sequencing identified compound heterozygous KCNJ1 gene mutations, c. 931C >T (p.R311W) and c. 445-446insCCTGAACAC (p.V149Afs, 150X), with the latter a novel mutation. Her father and mother were heterozygous carriers of c. 931C >T (p.R311W) and c. 445-446insCCTGAACAC (p.V149Afs, 150X), respectively. In conclusion, this case of BS type Ⅱ is caused by a novel compound heterozygous KCNJ1 mutation. Further studies are needed to verify the effect of celecoxib in BS patients.

Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two-phase study.

The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na+ /Ca2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (Pinteraction = 0.048). We found an inverse association between calcium intake (1000-2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G-allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1, and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30-57% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes when calcium intake was below 2500 mg/day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer.

A clinical and hereditary analysis of novel complex heterozygous KCNJ1 mutation in a Bartter syndrome type Ⅱ patient / 中华内科杂志

Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C ＞ T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C ＞ T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.

A clinical and hereditary analysis of novel complex heterozygous KCNJ1 mutation in a Bartter syndrome type Ⅱ patient / 中华内科杂志

Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C ＞ T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C ＞ T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.

Association between KCNJ11 polymorphism and essential hypertension in Xinjiang Kazak population / 西安交通大学学报(医学版)

Objective To investigate the relationship between the single nucleotide polymorphism (SNP)of KCNJ1 1 (inwardly rectifying potassium channel,subfamily J,member 1 1)gene and essential hypertension (EH)in Xinjiang Kazak population.Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP ) method was used to detect genotypes of rs2285676 polymorphism of KCNJ1 1, including 126 hypertensives (EH group)and 126 normotensives (NT group)in Xinjiang Kazak population.Multiple-factor unconditional Logistic regression analysis was used to evaluate the risk factors for hypertension in Xinjiang Kazak. Results Logistic regression analysis showed that KCNJ1 1-rs2285676 genotypes,sex,weight,total cholesterol and triglyceride were not associated with hypertension;body mass index (BMI)and high-density lipoprotein (HDL) were protective factors affecting hypertension while low-density lipoprotein (LDL ) was a risk factor for hypertension.Genotypes (TT,CT and CC)and allele frequencies (T and C)of the SNP of rs2285676 in KCNJ1 1 gene were 50.00%,48.41%,1.59%,74.21% and 25.79% in EH group,respectively.The differences between EH and normal control were not significant (P >0.05).Conclusion The rs2285676 polymorphism of KCNJ1 1 is not associated with EH in Xinjiang Kazak population.