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[PMID]:29178649
[Au] Autor:Eggermann T; Oehl-Jaschkowitz B; Dicks S; Thomas W; Kanber D; Albrecht B; Begemann M; Kurth I; Beygo J; Buiting K
[Ad] Endereço:Medical Faculty, Institute of Human Genetics, RWTH Aachen University, Aachen, Germany.
[Ti] Título:The maternal uniparental disomy of chromosome 6 (upd(6)mat) "phenotype": result of placental trisomy 6 mosaicism?
[So] Source:Mol Genet Genomic Med;5(6):668-677, 2017 11.
[Is] ISSN:2324-9269
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Maternal uniparental disomy of chromosome 6 (upd(6)mat) is a rare finding and its clinical relevance is currently unclear. Based on clinical data from two new cases and patients from the literature, the pathogenetic significance of upd(6)mat is delineated. METHODS: Own cases were molecularly characterized for isodisomic uniparental regions on chromosome 6. For further cases with upd(6)mat, a literature search was conducted and genetic and clinical data were ascertained. RESULTS: Comparison of isodisomic regions between the new upd(6)mat cases and those from four reports did not reveal any common isodisomic region. Among the patients with available cytogenetic data, five had a normal karyotype in lymphocytes, whereas a trisomy 6 (mosaicism) was detected prenatally in four cases. A common clinical picture was not obvious in upd(6)mat, but intrauterine growth restriction (IUGR) and preterm delivery were frequent. CONCLUSION: A common upd(6)mat phenotype is not obvious, but placental dysfunction due to trisomy 6 mosaicism probably contributes to IUGR and preterm delivery. In fact, other clinical features observed in upd(6)mat patients might be caused by homozygosity of recessive mutations or by an undetected trisomy 6 cell line. Upd(6)mat itself is not associated with clinical features, and can rather be regarded as a biomarker. In case upd(6)mat is detected, the cause for the phenotype is identified indirectly, but the UPD is not the basic cause.
[Mh] Termos MeSH primário: Cromossomos Humanos Par 6
Placenta/metabolismo
Trissomia/diagnóstico
Dissomia Uniparental/patologia
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Proteínas Culina/genética
Feminino
Retardo do Crescimento Fetal/diagnóstico
Retardo do Crescimento Fetal/genética
Testes Genéticos
Seres Humanos
Recém-Nascido
Cariótipo
Masculino
Mosaicismo
Análise de Sequência com Séries de Oligonucleotídeos
Fenótipo
Polimorfismo de Nucleotídeo Único
Gravidez
Nascimento Prematuro
Esteroide 21-Hidroxilase/genética
Trissomia/genética
Dissomia Uniparental/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (CUL7 protein, human); 0 (Cullin Proteins); EC 1.14.14.16 (CYP21A2 protein, human); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1002/mgg3.324


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[PMID]:28893623
[Au] Autor:Malikova J; Brixius-Anderko S; Udhane SS; Parween S; Dick B; Bernhardt R; Pandey AV
[Ad] Endereço:Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Inselspital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.
[Ti] Título:CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2.
[So] Source:J Steroid Biochem Mol Biol;174:192-200, 2017 Nov.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1µM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2. Cells were treated with varying concentrations of abiraterone for 24h and CYP21A2 activity was measured using [ H] 17-hydroxyprogesterone as substrate. Whole steroid profile changes were determined by gas chromatography-mass spectrometry. Binding of abiraterone to purified CYP21A2 protein was measured spectroscopically. Computational docking was used to study the binding and interaction of abiraterone with CYP21A2. Abiraterone caused significant reduction in CYP21A2 activity in assays with cells and an inhibition of CYP21A2 activity was also observed in experiments using recombinant purified proteins. Abiraterone binds to CYP21A2 with an estimated Kd of 6.3µM. These inhibitory effects of abiraterone are at clinically used concentrations. A loss of CYP21A2 activity in combination with reduction of CYP17A1 activities by abiraterone could result in lower cortisol levels and may require monitoring for any potential adverse effects.
[Mh] Termos MeSH primário: Androstenos/farmacologia
Antineoplásicos/farmacologia
Esteroide 21-Hidroxilase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Escherichia coli/genética
Seres Humanos
Masculino
Simulação de Acoplamento Molecular
Neoplasias da Próstata
Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores
Esteroide 21-Hidroxilase/química
Esteroide 21-Hidroxilase/genética
Esteroide 21-Hidroxilase/metabolismo
Esteroides/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstenes); 0 (Antineoplastic Agents); 0 (Steroids); EC 1.14.14.16 (CYP21A2 protein, human); EC 1.14.14.16 (Steroid 21-Hydroxylase); EC 1.14.14.19 (CYP17A1 protein, human); EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase); G819A456D0 (abiraterone)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE


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[PMID]:28844486
[Au] Autor:Vermeulen C; Geeven G; de Wit E; Verstegen MJAM; Jansen RPM; van Kranenburg M; de Bruijn E; Pulit SL; Kruisselbrink E; Shahsavari Z; Omrani D; Zeinali F; Najmabadi H; Katsila T; Vrettou C; Patrinos GP; Traeger-Synodinos J; Splinter E; Beekman JM; Kheradmand Kia S; Te Meerman GJ; Ploos van Amstel HK; de Laat W
[Ad] Endereço:Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
[Ti] Título:Sensitive Monogenic Noninvasive Prenatal Diagnosis by Targeted Haplotyping.
[So] Source:Am J Hum Genet;101(3):326-339, 2017 Sep 07.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During pregnancy, cell-free DNA (cfDNA) in maternal blood encompasses a small percentage of cell-free fetal DNA (cffDNA), an easily accessible source for determination of fetal disease status in risk families through non-invasive procedures. In case of monogenic heritable disease, background maternal cfDNA prohibits direct observation of the maternally inherited allele. Non-invasive prenatal diagnostics (NIPD) of monogenic diseases therefore relies on parental haplotyping and statistical assessment of inherited alleles from cffDNA, techniques currently unavailable for routine clinical practice. Here, we present monogenic NIPD (MG-NIPD), which requires a blood sample from both parents, for targeted locus amplification (TLA)-based phasing of heterozygous variants selectively at a gene of interest. Capture probes-based targeted sequencing of cfDNA from the pregnant mother and a tailored statistical analysis enables predicting fetal gene inheritance. MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict the inherited alleles with >98% confidence, even at relatively early stages (8 weeks) of pregnancy. This prediction and the accuracy of parental haplotyping was confirmed by sequencing of fetal material obtained by parallel invasive procedures. MG-NIPD is a robust method that requires standard instrumentation and can be implemented in any clinic to provide families carrying a severe monogenic disease with a prenatal diagnostic test based on a simple blood draw.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/diagnóstico
Biomarcadores/sangue
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Fibrose Cística/diagnóstico
Polimorfismo de Nucleotídeo Único
Diagnóstico Pré-Natal/métodos
Esteroide 21-Hidroxilase/genética
[Mh] Termos MeSH secundário: Hiperplasia Suprarrenal Congênita/sangue
Hiperplasia Suprarrenal Congênita/genética
Células Cultivadas
Fibrose Cística/sangue
Fibrose Cística/genética
Regulador de Condutância Transmembrana em Fibrose Cística/sangue
DNA/sangue
DNA/genética
Feminino
Haplótipos
Seres Humanos
Gravidez
Esteroide 21-Hidroxilase/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (CFTR protein, human); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 9007-49-2 (DNA); EC 1.14.14.16 (CYP21A2 protein, human); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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[PMID]:28707538
[Au] Autor:Michelle M A; Jensen CT; Habra MA; Menias CO; Shaaban AM; Wagner-Bartak NA; Roman-Colon AM; Elsayes KM
[Ad] Endereço:1 Department of Diagnostic Radiology, Baylor College of Medicine, Houston, TX, USA.
[Ti] Título:Adrenal cortical hyperplasia: diagnostic workup, subtypes, imaging features and mimics.
[So] Source:Br J Radiol;90(1079):20170330, 2017 Nov.
[Is] ISSN:1748-880X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.
[Mh] Termos MeSH primário: Glândulas Suprarrenais/diagnóstico por imagem
Hiperplasia Suprarrenal Congênita/diagnóstico
[Mh] Termos MeSH secundário: Adolescente
Glândulas Suprarrenais/patologia
Hiperplasia Suprarrenal Congênita/classificação
Hiperplasia Suprarrenal Congênita/diagnóstico por imagem
Hiperplasia Suprarrenal Congênita/metabolismo
Hormônio Adrenocorticotrópico/sangue
Adulto
Síndrome de Cushing/diagnóstico
Diagnóstico Diferencial
Feminino
Seres Humanos
Hiperplasia/classificação
Hiperplasia/diagnóstico por imagem
Hiperplasia/etiologia
Recém-Nascido
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Tamanho do Órgão
Hipersecreção Hipofisária de ACTH/diagnóstico
Esteroide 21-Hidroxilase
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
9002-60-2 (Adrenocorticotropic Hormone); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1259/bjr.20170330


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[PMID]:28542000
[Au] Autor:Besnier E; Clavier T; Tonon MC; Selim J; Lefevre-Scelles A; Morin F; Tamion F; Dureuil B; Castel H; Compere V
[Ad] Endereço:From the Department of Anesthesia and Critical Care (E.B., T.C., J.S., A.L.-S., B.D., V.C.) and the Medical Critical Care Unit (F.T.), Normandy University, UNIROUEN (Rouen University), Rouen University Hospital, Rouen, France; Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Normandy University, UNIROUEN, INSERM (Institut National de la Santé Et de la Recherche Médicale) U982, Rouen, France (E.B., T.C., M.-C.T., A.L.-S., F.M., H.C., V.C.); Institute for Research and Innovation in Biomedicine, Rouen, France (E.B., T.C., M.-C.T., J.S., A.L.-S., F.M., F.T., H.C., V.C.); and the Department of Pharmacology, Normandy University, UNIROUEN, INSERM U1096, Rouen, France (J.S., F.T.).
[Ti] Título:Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model.
[So] Source:Anesthesiology;127(2):347-354, 2017 Aug.
[Is] ISSN:1528-1175
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis. METHODS: Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3ß-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11ß-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD). RESULTS: At 12 h, lipopolysaccharide induced an overexpression of corticotropin-releasing hormone (32 ± 5 vs. 18 ± 6, P < 0.01), proopiomelanocortin (21 ± 3 vs. 8 ± 0.9, P < 0.0001), P450 side-chain cleavage (32 ± 4 vs. 23 ± 10, P < 0.05), 21-hydroxylase (17 ± 5 vs. 12 ± 2, P < 0.05), and 11ß-hydroxylase (11 ± 4 vs. 6 ± 0.5, P = 0.001), and an elevation of corticosterone (642 ± 165 vs. 98.3 ± 63 ng/ml, P < 0.0001). Etomidate and ketamine reduced P450 side-chain cleavage (19 ± 7 and 19 ± 3 vs. 32 ± 4, P < 0.01), 21-hydroxylase (8 ± 0.8 and 8 ± 1 vs. 17 ± 5, P < 0.001), 11ß-hydroxylase (4 ± 0.5 and 7 ± 1 vs. 11 ± 4, P < 0.001 and P < 0.05), and corticosterone (413 ± 189 and 260 ± 161 vs. 642 ± 165 ng/ml, P < 0.05 and P < 0.01). Ketamine also inhibited adrenocorticotropin hormone production (2.5 ± 3.6 vs. 36 ± 15 pg/ml, P < 0.05). At 48 h, all four adrenal enzymes were down-regulated by lipopolysaccharide administration with corticosterone levels similar to the control group. Ketamine and etomidate did not modify corticosterone plasma levels. CONCLUSIONS: Our endotoxemic model induces an initial activation of the hypothalamic-pituitary-adrenal axis, followed by a secondary inhibition of adrenal steroidogenesis processes. Ketamine and etomidate inhibit the enzyme expression and activity of the adrenal gland at the early stage.
[Mh] Termos MeSH primário: Regulação para Baixo/efeitos dos fármacos
Endotoxemia
Etomidato/farmacologia
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos
Ketamina/farmacologia
Sistema Hipófise-Suprarrenal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Analgésicos/farmacologia
Animais
Corticosterona/sangue
Hormônio Liberador da Corticotropina/sangue
Hormônio Liberador da Corticotropina/efeitos dos fármacos
Modelos Animais de Doenças
Etomidato/sangue
Hipnóticos e Sedativos/farmacologia
Sistema Hipotálamo-Hipofisário/fisiopatologia
Ketamina/sangue
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Sistema Hipófise-Suprarrenal/fisiopatologia
Pró-Opiomelanocortina/sangue
Pró-Opiomelanocortina/efeitos dos fármacos
Esteroide 21-Hidroxilase/sangue
Esteroide 21-Hidroxilase/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Hypnotics and Sedatives); 66796-54-1 (Pro-Opiomelanocortin); 690G0D6V8H (Ketamine); 9015-71-8 (Corticotropin-Releasing Hormone); EC 1.14.14.16 (Steroid 21-Hydroxylase); W980KJ009P (Corticosterone); Z22628B598 (Etomidate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1097/ALN.0000000000001704


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[PMID]:28539365
[Au] Autor:Wang C; Pallan PS; Zhang W; Lei L; Yoshimoto FK; Waterman MR; Egli M; Guengerich FP
[Ad] Endereço:From the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
[Ti] Título:Functional analysis of human cytochrome P450 21A2 variants involved in congenital adrenal hyperplasia.
[So] Source:J Biol Chem;292(26):10767-10778, 2017 Jun 30.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxyprogesterone (17α-OH-progesterone) to 11-deoxycortisol. More than 100 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of WT human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH-progesterone). We found that the 17α-OH-progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions. Twelve P450 21A2 variants associated with either salt-wasting or nonclassical forms of CAH were expressed, purified, and analyzed. The catalytic activities of these 12 variants ranged from 0.00009% to 30% of WT P450 21A2 and the extent of heme incorporation from 10% to 95% of the WT. Substrate dissociation constants ( ) for four variants were 37-13,000-fold higher than for WT P450 21A2. Cytochrome , which augments several P450 activities, inhibited P450 21A2 activity. Similar to the WT enzyme, high noncompetitive intermolecular kinetic deuterium isotope effects (≥ 5.5) were observed for all six P450 21A2 variants examined for 21-hydroxylation of 21- -progesterone, indicating that C-H bond breaking is a rate-limiting step over a 10 -fold range of catalytic efficiency. Using UV-visible and CD spectroscopy, we found that P450 21A2 thermal stability assessed in bacterial cells and with purified enzymes differed among salt-wasting- and nonclassical-associated variants, but these differences did not correlate with catalytic activity. Our in-depth investigation of CAH-associated P450 21A2 variants reveals critical insight into the effects of disease-causing mutations on this important enzyme.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/enzimologia
Mutação
Esteroide 21-Hidroxilase/química
[Mh] Termos MeSH secundário: Hiperplasia Suprarrenal Congênita/genética
Dicroísmo Circular
Citocromos b5/química
Citocromos b5/genética
Citocromos b5/metabolismo
Medição da Troca de Deutério
Estabilidade Enzimática
Temperatura Alta
Seres Humanos
Domínios Proteicos
Espectrofotometria Ultravioleta
Esteroide 21-Hidroxilase/genética
Esteroide 21-Hidroxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9035-39-6 (Cytochromes b5); EC 1.14.14.16 (CYP21A2 protein, human); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170715
[Lr] Data última revisão:
170715
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.792465


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[PMID]:28521877
[Au] Autor:Concolino P; Rizza R; Costella A; Carrozza C; Zuppi C; Capoluongo E
[Ad] Endereço:Laboratory of Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy. Electronic address: paola.concolino@policlinicogemelli.it.
[Ti] Título:CYP21A2 intronic variants causing 21-hydroxylase deficiency.
[So] Source:Metabolism;71:46-51, 2017 Jun.
[Is] ISSN:1532-8600
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase gene (CYP21A2). Most of CYP21A2 mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5-10% of 21-hydroxylase deficiency alleles. Intronic variants represent only a little part of these but their effect on the protein is generally deleterious. The aim of this paper is to provide a comprehensive literary review regarding all intronic CYP21A2 pathological variants reported to date. In addition, we describe three novel causing disease variants in our patients affected by the classic form of CAH: IVS4-1G>A, IVS5-8T>A, IVS8-2A>G. In silico analysis revealed that all these substitutions affect the splicing process leading to a non-functional protein. Based on these results, we are able to classify them as pathological variants according to the patient's phenotype.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/genética
Esteroide 21-Hidroxilase/genética
[Mh] Termos MeSH secundário: Variação Genética
Seres Humanos
Íntrons/genética
Patologia Molecular
Esteroide 21-Hidroxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
EC 1.14.14.16 (CYP21A2 protein, human); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE


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[PMID]:28415939
[Au] Autor:Zhang B; Lu L; Lu Z
[Ad] Endereço:1 Department of Endocrinology, China - Japan Friendship Hospital, Beijing, China.
[Ti] Título:Molecular diagnosis of Chinese patients with 21-hydroxylase deficiency and analysis of genotype-phenotype correlations.
[So] Source:J Int Med Res;45(2):481-492, 2017 Apr.
[Is] ISSN:1473-2300
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objective The spectrum of molecular defects in Chinese patients with 21-hydroxylase deficiency (21-OHD), and genotype-phenotype relationships are unknown. Methods We screened eight patients with non-classical (NC) 21-OHD and 35 with classical 21-OHD, and detected nine known mutations. Results The most frequent mutation among the 43 21-OHD cases was p.Ile172Asn (allele frequency, 36.0%), followed by c.290-13A/C > G (20.9%), Del (8.6%), p.Pro30Leu (7.0%), p.Gln318Ter (7.0%), p.Val281Leu (4.7%), p.Arg356Trp (2.3%), p.[Ile236Asn; Val237Glu; Met239Lys] (2.3%), and E3Δ8 bp (1.2%). The frequency spectrum of CYP21A2 mutations in the Chinese population was similar to that in the Japanese population, except that p.Val281Leu was identified in Chinese NC21-OHD patients at a frequency of 25.0%, whereas it was absent in Japanese patients. We found that genotype could predict phenotype in 88.3% of patients. Conclusion Some characteristics appear to be unique to the Chinese population, but genotype was strongly predictive of phenotype.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/diagnóstico
Hiperplasia Suprarrenal Congênita/genética
Estudos de Associação Genética
Mutação
Esteroide 21-Hidroxilase/genética
[Mh] Termos MeSH secundário: Hiperplasia Suprarrenal Congênita/etnologia
Hiperplasia Suprarrenal Congênita/patologia
Adulto
Alelos
Grupo com Ancestrais do Continente Asiático
Criança
Pré-Escolar
Feminino
Expressão Gênica
Frequência do Gene
Estudo de Associação Genômica Ampla
Genótipo
Seres Humanos
Masculino
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1177/0300060516685204


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[PMID]:28401898
[Au] Autor:Doleschall M; Luczay A; Koncz K; Hadzsiev K; Erhardt É; Szilágyi Á; Doleschall Z; Németh K; Török D; Prohászka Z; Gereben B; Fekete G; Gláz E; Igaz P; Korbonits M; Tóth M; Rácz K; Patócs A
[Ad] Endereço:Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
[Ti] Título:A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics.
[So] Source:Eur J Hum Genet;25(6):702-710, 2017 Jun.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/genética
Variações do Número de Cópias de DNA
Esteroide 21-Hidroxilase/genética
[Mh] Termos MeSH secundário: Glândulas Suprarrenais/metabolismo
Hiperplasia Suprarrenal Congênita/patologia
Evolução Molecular
Feminino
Haplótipos
Seres Humanos
Masculino
Esteroide 21-Hidroxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.14.16 (CYP21A2 protein, human); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2017.38


  10 / 1661 MEDLINE  
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[PMID]:28383228
[Au] Autor:Nermoen I; Husebye ES; Myhre AG; Løvås K
[Ad] Endereço:Endokrinologisk avdeling Akershus universitetssykehus og Campus Ahus Institutt for klinisk medisin Universitetet i Oslo.
[Ti] Título:Classic congenital adrenal hyperplasia.
[Ti] Título:Klassisk medfødt binyrebarkhyperplasi..
[So] Source:Tidsskr Nor Laegeforen;137(7):540-543, 2017 Apr.
[Is] ISSN:0807-7096
[Cp] País de publicação:Norway
[La] Idioma:eng; nor
[Ab] Resumo:Congenital adrenal hyperplasia is attributed to inherited enzyme defects in the adrenal cortex. The classical form results in reduced production of cortisol and aldosterone, accompanied by an increase in production of adrenal cortical androgens. This causes virilisation in girls, adrenocortical failure and early puberty in both sexes. This article describes the genetics, clinical picture, diagnostics and treatment.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita
[Mh] Termos MeSH secundário: Hiperplasia Suprarrenal Congênita/complicações
Hiperplasia Suprarrenal Congênita/diagnóstico
Hiperplasia Suprarrenal Congênita/tratamento farmacológico
Hiperplasia Suprarrenal Congênita/genética
Feminino
Glucocorticoides/administração & dosagem
Glucocorticoides/uso terapêutico
Seres Humanos
Masculino
Puberdade Precoce/etiologia
Esteroide 21-Hidroxilase/genética
Virilismo/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Glucocorticoids); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.4045/tidsskr.16.0376



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