目的:探讨醛固酮瘤中CYP11B2,CYP11B1基因多态性与CYP11B2基因mRNA表达及术前血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。方法:20例正常肾上腺和69例醛固酮瘤组织标本,分别取自2006年5月～2007年11月在华中科技大学同济医学院附...目的:探讨醛固酮瘤中CYP11B2,CYP11B1基因多态性与CYP11B2基因mRNA表达及术前血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。方法:20例正常肾上腺和69例醛固酮瘤组织标本,分别取自2006年5月～2007年11月在华中科技大学同济医学院附属同济医院泌尿外科行肾癌根治术和肾上腺手术切除的患者。采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性(野生型/转位型)。采用syb greenReal time RT-PCR检测CYP11B2基因mRNA表达。在Rstatistics program 2.7.0程序包中使用SNPassoc 1.5-3和Haplo.stats 1.3.8分析CYP11B2和CYP11B1基因多态性及单体型与CYP11B2基因表达量和血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。结果:单体型分型中,Global Score统计显示:CYP11B2-CYP11B1单体型与CYP11B2mRNA表达量增加相关(global-stat=16.175,df=8,P=0.04),与血清醛固酮水平相关(global-stat=20.407,df=8,P=0.009)。但与收缩压和舒张压不相关(分别P=0.34,P=0.54);多元回归分析中发现单体型H1(AGAConvT)和H3(AGAWtC)与CYP11B2基因mRNA的表达上调相关(经过Bonferroni校正后分别P=0.002;P=0.003),而H6(AGGWtT)、H10(AAAWtT)和H16(GAAWtT)与过多的醛固酮分泌相关(经过Bonferroni校正后分别P<0.0005;P=0.002;P=0.0015);但未见有单体型与收缩压和舒张压相关(均P>0.05)。结论:CYP11B2和CYP11B1基因多态性可能通过上调CYP11B2的表达,导致醛固酮瘤患者血清醛固酮水平的升高。展开更多
Background Steroid 11β-hydroxylase deficiency （11β-OHD）, an autosomal recessive inherited disease, accounts for 5%-8% of congenital adrenal hyperplasia. It was scarcely reported in China. This article reports two ...Background Steroid 11β-hydroxylase deficiency （11β-OHD）, an autosomal recessive inherited disease, accounts for 5%-8% of congenital adrenal hyperplasia. It was scarcely reported in China. This article reports two Chinese girls with 11β-OHD. Methods The two patients were sisters and presented with hypertrichosis, skin pigmentation, laryngeal prominence and virilization of external genitalia. The patients were followed up for their clinical symptoms and signs, hormone profile, and adrenal image. The genomic deoxyribonucleic acids of the patients and their parents were isolated. 11β-hydroxylase gene （CYP11B1） was amplified by polymerase chain reaction and directly sequenced. Results Hormone tests showed that serum cortisol was in the low limit of normal range, whereas the concentrations of adrenocorticotropic hormone, testosterone and progesterone were much higher than those of normal adult females. There were obvious adrenal hyperplasia and advance of bone age. After 11 months of treatment with dexamethasone, the skin pigment became regressed; the breast, uterus and ovary gradually developed and normal menstrual cycle started while the manifestations of virilization did not change. A single point mutation of CYP11B1 （R454C, GGC → TGC） in all the members of this family was detected. The sisters were homozygous and their parents were heterozygous. Conclusions The clinical manifestation of 11β-OHD is complicated. The manifestation of virilization could not regress after treatment with dexamethasone. The novel missense mutation of CYP11B1 （R454C, GGC → TGC） is the pathogenesis of 11β-OHD at least in some Chinese patients.展开更多
White P C等[1]于1991年首次报道CYP11B1基因突变引起11β-羟化酶缺陷症(11β-hydroxylase deficiency,11β-OHD)以来,最新研究表明11β-OHD占先天性肾上腺皮质增生症(congennital adrenal hyperplasia,CAH)的0.2%~8.0%,在普通人群中发...White P C等[1]于1991年首次报道CYP11B1基因突变引起11β-羟化酶缺陷症(11β-hydroxylase deficiency,11β-OHD)以来,最新研究表明11β-OHD占先天性肾上腺皮质增生症(congennital adrenal hyperplasia,CAH)的0.2%~8.0%,在普通人群中发病率为1/9000000[2-4],而在从摩洛哥移民到以色列的犹太人群中,该病在新生儿中的发病率高达1/7000~1/5000[5],不同的地区及种群发病率不同,其在中东和北非等地区发病率最高[6]。展开更多
Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase deficiency.For this study,we investigated the relationship between the clin...Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase deficiency.For this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia.Methods Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed.We examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of proteins.Results We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were reported.Female patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 years.The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>T.All mutations lead to spatial conformational changes that affect protein stability.Conclusions Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations.Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations.The correlation between genotype and phenotype needs further study.Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.展开更多
文摘目的:探讨醛固酮瘤中CYP11B2,CYP11B1基因多态性与CYP11B2基因mRNA表达及术前血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。方法:20例正常肾上腺和69例醛固酮瘤组织标本,分别取自2006年5月～2007年11月在华中科技大学同济医学院附属同济医院泌尿外科行肾癌根治术和肾上腺手术切除的患者。采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性(野生型/转位型)。采用syb greenReal time RT-PCR检测CYP11B2基因mRNA表达。在Rstatistics program 2.7.0程序包中使用SNPassoc 1.5-3和Haplo.stats 1.3.8分析CYP11B2和CYP11B1基因多态性及单体型与CYP11B2基因表达量和血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。结果:单体型分型中,Global Score统计显示:CYP11B2-CYP11B1单体型与CYP11B2mRNA表达量增加相关(global-stat=16.175,df=8,P=0.04),与血清醛固酮水平相关(global-stat=20.407,df=8,P=0.009)。但与收缩压和舒张压不相关(分别P=0.34,P=0.54);多元回归分析中发现单体型H1(AGAConvT)和H3(AGAWtC)与CYP11B2基因mRNA的表达上调相关(经过Bonferroni校正后分别P=0.002;P=0.003),而H6(AGGWtT)、H10(AAAWtT)和H16(GAAWtT)与过多的醛固酮分泌相关(经过Bonferroni校正后分别P<0.0005;P=0.002;P=0.0015);但未见有单体型与收缩压和舒张压相关(均P>0.05)。结论:CYP11B2和CYP11B1基因多态性可能通过上调CYP11B2的表达,导致醛固酮瘤患者血清醛固酮水平的升高。
文摘Background Steroid 11β-hydroxylase deficiency （11β-OHD）, an autosomal recessive inherited disease, accounts for 5%-8% of congenital adrenal hyperplasia. It was scarcely reported in China. This article reports two Chinese girls with 11β-OHD. Methods The two patients were sisters and presented with hypertrichosis, skin pigmentation, laryngeal prominence and virilization of external genitalia. The patients were followed up for their clinical symptoms and signs, hormone profile, and adrenal image. The genomic deoxyribonucleic acids of the patients and their parents were isolated. 11β-hydroxylase gene （CYP11B1） was amplified by polymerase chain reaction and directly sequenced. Results Hormone tests showed that serum cortisol was in the low limit of normal range, whereas the concentrations of adrenocorticotropic hormone, testosterone and progesterone were much higher than those of normal adult females. There were obvious adrenal hyperplasia and advance of bone age. After 11 months of treatment with dexamethasone, the skin pigment became regressed; the breast, uterus and ovary gradually developed and normal menstrual cycle started while the manifestations of virilization did not change. A single point mutation of CYP11B1 （R454C, GGC → TGC） in all the members of this family was detected. The sisters were homozygous and their parents were heterozygous. Conclusions The clinical manifestation of 11β-OHD is complicated. The manifestation of virilization could not regress after treatment with dexamethasone. The novel missense mutation of CYP11B1 （R454C, GGC → TGC） is the pathogenesis of 11β-OHD at least in some Chinese patients.
文摘Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase deficiency.For this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia.Methods Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed.We examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of proteins.Results We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were reported.Female patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 years.The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>T.All mutations lead to spatial conformational changes that affect protein stability.Conclusions Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations.Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations.The correlation between genotype and phenotype needs further study.Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.
