OBJECTIVE: To analyze a child with 11β hydroxylase deficiency (11β-OHD) due to CYP11B2/CYP11B1 chimeric gene. METHODS: Clinical data of the child who was admitted to Henan Children's Hospital on August 24, 2020 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene. RESULTS: The patient, a 5-year-old male, had featured premature development of secondary sex characteristics and accelerated growth, and was diagnosed with 21 hydroxylase deficiency (21-OHD). WES revealed that he has harbored a heterozygous c.1385T>C (p.L462P) variant of the CYP11B1 gene, in addition to a 37.02 kb deletion on 8q24.3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1385T>C (p.L462P) was rated as a likely pathogenic variant (PM2_Supporting+PP3_Moderate+PM3+PP4). The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene. The patient was diagnosed as 11β-OHD and effectively treated with hydrocortisone and triptorelin. A healthy fetus was delivered following genetic counseling and prenatal diagnosis. CONCLUSION 11β-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene, which will require multiple methods for the detection.
Child, Preschool ; Humans ; Male ; Adrenal Hyperplasia, Congenital/genetics* ; Cytochrome P-450 CYP11B2/genetics* ; Exons ; Retrospective Studies ; Steroid 11-beta-Hydroxylase/genetics*

OBJECTIVE: To analyze the clinical characteristics and genetic variants in a two-month-and-one-day male infant with aldosterone synthase deficiency. METHODS: Clinical data of the child was collected. Whole exome sequencing was carried out by next generation sequencing(NGS). Candidate variants were verified by Sanger sequencing. RESULTS: The infant had measured 54 cm (-2.1 SD) in length and 3.9 kg (-2.8 SD) in weight, and featured recurrent vomiting, poor feeding, apathetic appearance and failure to thrive. Blood electrolyte testing showed low sodium and increased potassium. Serum cortisol, adrenocorticotrophic hormone, 17-alpha-hydroxyl progesterone, androstenedione, and testosterone were all within the normal ranges. The plasma renin activity activity was increased, and plasma aldosterone level was low. NGS revealed that the infant has harbored compound heterozygous variants of the CYP11B2 gene, namely c.1334T>G(p.Phe445Cys) inherited from his father and c.1121G>A(p.Arg374Gln) inherited from his mother. Neither variant was reported previously, and both were predicted to be deleterious for the function of the protein product. CONCLUSION The compound heterozygous variants of c.1334T>G (p.Phe445Cys) and c.1121G>A (p.Arg374Gln) of the CYP11B2 gene probably underlay the disease in this patient.
Child ; Cytochrome P-450 CYP11B2/genetics* ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Mutation ; Whole Exome Sequencing

It has been proven that familial aldosteronism type I is related to 11-beta hydroxylase (CYP11B1)/aldosterone synthase (CYP11B2) chimeric genes. In recent years, accumulated evidences indicate that the genetic basis of primary aldosteronism may involve chromosome 7p22 candidate genes, polymorphisms of CYP11B1 and CYP11B2 genes, mutations of ion channel- related KCNJ5, ATP1A1, CACNA1D genes. The article reviews the progress on genetic basis of primary aldosteronism.
Cytochrome P-450 CYP11B2 ; genetics ; Humans ; Hyperaldosteronism ; genetics ; Mutation ; Polymorphism, Genetic ; Steroid 11-beta-Hydroxylase ; genetics

<p>OBJECTIVETo evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension.p><p>METHODSEight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender.p><p>RESULTSA total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent.p><p>CONCLUSIONIn males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.p>
Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Humans ; Hydrochlorothiazide ; pharmacology ; Hypertension ; drug therapy ; enzymology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Renin-Angiotensin System ; drug effects ; genetics

<p>OBJECTIVETo explore the relationship between the -344T/C polymorphism of aldosterone synthase (CYP11B2) gene and essential hypertension in Chinese Mongolian population.p><p>METHODSBy cluster-sampling method, a total of 1575 Mongolian people in Tongliao city of Inner Mongolia were included in this study. And 417 subjects were normotension, 596 subjects were prehypertension and 562 subjects were essential hypertension. A survey was conducted to collect data by personal interview using a standard questionnaire, meanwhile fasting blood samples were drawn. Height, weight, waist circumference, blood pressure, blood-fat indexes and fasting plasma glucose were measured. The variant genotypes of CYP11B2 were identified by PCR assays. The relationship between the -344T/C polymorphism of CYP11B2 gene and essential hypertension were analyzed by multinomial logistic regression model.p><p>RESULTSCrude prevalence of prehypertension among Mongolian people was 37.84% (596/1575) and hypertension was 35.68% (562/1575). The age-standardized prevalence of prehypertension was 38.57% and hypertension was 31.53%. The frequency of the T and C allele was 0.66 (481/728) and 0.34 (247/728) for normotension group, 0.69 (696/1042) and 0.33 (346/1042) for prehypertension group, 0.71 (706/998) and 0.29 (292/998) for hypertension group. The multiple logistic models showed CYP11B2 variant genotypes were associated with prehypertension (TT/CC, OR = 1.33, 95%CI: 0.87 - 2.01; TC/CC, OR = 1.74, 95%CI: 1.13 - 2.67; TC + TT/CC, OR = 1.49, 95%CI: 1.01 - 2.22); CYP11B2 variant genotypes were associated with hypertension (TT/CC, OR = 1.70, 95%CI: 1.07 - 2.70; TC/CC, OR = 1.59, 95%CI: 0.98 - 2.50; TC + TT/CC, OR = 1.66, 95%CI: 1.06 - 2.58).p><p>CONCLUSIONCYP11B2 gene -344T/C polymorphism were associated with essential hypertension in Chinese Mongolian population.p>
Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; China ; epidemiology ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Young Adult

<p>BACKGROUNDGenetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, the aldosterone synthase (CYP11B2) gene, C-344T, and the angiotensin II type 1 receptor (AT1R) gene, A1166C, have been shown to be associated with IgA nephropathy (IgAN) and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease (ESRD) and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD.p><p>METHODSGenotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected.p><p>RESULTSACE, AGT, CYP and AT1R genotype distributions were similar in patients with IgAN and in controls. Comparing patients with ESRD (IgAN-ESRD) and those without ESRD (IgAN-non ESRD), there was a significant increase only in the ACE DD genotype (P < 0.05) among the four gene polymorphisms. There was significant dominance of the male (P < 0.05), more marked hypertension (P < 0.01), proteinuria (P < 0.01) and increased serum creatinine during renal biopsy (P < 0.01) in the IgAN-ESRD group.p><p>CONCLUSIONAmong the ACE, AGT, AT1R and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.p>
Adult ; Angiotensinogen ; genetics ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Glomerulonephritis, IGA ; genetics ; Humans ; Kidney Failure, Chronic ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; genetics ; Receptor, Angiotensin, Type 1 ; genetics ; Renin-Angiotensin System ; genetics

<p>OBJECTIVETo investigate whether the -344T/C polymorphism of aldosterone synthase gene is associated with early renal damage in Han nationality with essential hypertension in Shandong province.p><p>METHODSPlasma aldosterone concentration and urinary albumin excretion were measured with radioimmunoassays in 225 patients with essential hypertension, and hypertensives were classified as hypertension with normal albuminuria or hypertension with microalbuminuria according to urinary albumin excretion during 24 hours. -344T/C polymorphism of aldosterone synthase gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in controls and hypertensives.p><p>RESULTSNo significant differences were found in genotype distribution among groups of control, primary hypertension with normal albuminuria and hypertension with microalbuminuria. The C allele frequency in hypertension with microal buminuria group was significantly higher than that in control and hypertension with normal albuminuria group (P < 0.05). In hypertensive patients, plasma aldosterone concentration and urinary albumin excretion of TC+CC genotypes were significantly higher than that of TT genotype ( P< 0.05).p><p>CONCLUSIONThese results suggest that -344T/C polymorphism of aldosterone synthase gene may be associated with early renal damage in Han nationality with essential hypertension, C allele may be a genetic factor susceptible to renal damage in hypertensives.p>
Adult ; Albumins ; metabolism ; Albuminuria ; blood ; genetics ; Aldosterone ; blood ; Asian Continental Ancestry Group ; genetics ; China ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genotype ; Humans ; Hypertension ; blood ; complications ; Kidney Diseases ; complications ; ethnology ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; genetics ; Radioimmunoassay

<p>OBJECTIVETo explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene (CYP11B2) and the incidence of essential hypertension in a northern Chinese Han population.p><p>METHODSWe conducted a case-control study including 182 hypertensive patients and 189 healthy controls in Harbin newspaper office and assayed the genotypes of C-344T and K173R using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technology.p><p>RESULTSThe distributions of C-344T and K173R genotype frequencies in men and women were in accordance with the Hardy-Weinberg equilibrium. The differences of C-344T allele and genotype as well as K173R allele frequency distributions between hypertensive patients and healthy controls were not statistically significant in men and women and pooled population (P > or = 0.05). The difference of K173R genotype frequency distribution reached borderline significance (P = 0.0500) and was more pronounced in women (P = 0.0038) according to the dominant mode of inheritance. Moreover, the magnitude of this mode of inheritance was more remarkable after the confounding factors were adjusted. K173R statistically correlated with the systolic hypertension in women.p><p>CONCLUSIONThe CYP11B2 K173R polymorphism correlates with the susceptibility of essential hypertension in the northern Chinese Han population.p>
Asian Continental Ancestry Group ; Case-Control Studies ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Hypertension ; genetics ; Male ; Polymorphism, Genetic

<p>BACKGROUNDThe renin-angiotensin-aldosterone system (RAAS) is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP) response to diuretic treatment in a Chinese Han ethnic population.p><p>METHODSFifty-four patients with essential hypertension received hydrochlorothiazide (12.5 mg, once daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment.p><p>RESULTSThe patients with angiotensinogen (AGT) -6G allele showed a greater reduction in diastolic BP (P=0.025) and mean BP (P=0.039) than those carrying AA genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes (systolic BP: P=0.030; diastolic BP: P=0.026; mean BP: P=0.003). In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes (P=0.007).p><p>CONCLUSIONSAGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.p>
Aged ; Angiotensinogen ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genotype ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide

<p>OBJECTIVETo investigate the relationship of associating the polymorphisms of CYP11B2 -344C/T and Hind III restriction site on Y chromosome with essential hypertension.p><p>METHODSThis study enrolled 654 patients with essential hypertension and 386 healthy subjects as control group. The genomic DNA was extracted from blood leukocytes. The DNA segments of CYP11B2 and Y chromosome were amplified from genomic DNA by polymerase chain reaction (PCR). The PCR products were digested with Hae III or Hind III at 37 degrees centigrade respectively. The digested products were subjected to agarose gel electrophoresis and stain with ethidium bromide.p><p>RESULTS(1)The Hind III (-) genotype was found at 42.0% for patients with essential hypertension and 32.9% for control. The Hind III (-) genotype frequency of hypertension patient was significantly higher than that of the control (P was 0.03). The Hind III (+) genotype had a lower SBP and DBP than the Hind III (-) genotype (P was 0.01, P was 0.03). (2)With combining CC or CT genotype with Hind III (-) genotype, the relative risk suffering from hypertension was 1.998 fold high (P was 0.01).p><p>CONCLUSIONThe polymorphism of Hind III restriction site on Y chromosome is associated with essential hypertension, and when combined with polymorphism of CYP11B2 -344C/T, may have a united role to increase the risk of suffering from hypertension disease.p>
Adult ; Aged ; Alleles ; Binding Sites ; genetics ; Chromosomes, Human, Y ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Deoxyribonuclease HindIII ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics