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[PMID]:28719049
[Au] Autor:Prosnitz AR; Leopold J; Irons M; Jenkins K; Roberts AE
[Ad] Endereço:Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
[Ti] Título:Pulmonary vein stenosis in patients with Smith-Lemli-Opitz syndrome.
[So] Source:Congenit Heart Dis;12(4):475-483, 2017 Jul.
[Is] ISSN:1747-0803
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To describe a group of children with co-incident pulmonary vein stenosis and Smith-Lemli-Opitz syndrome and to generate hypotheses as to the shared pathogenesis of these disorders. DESIGN: Retrospective case series. PATIENTS: Five subjects in a pulmonary vein stenosis cohort of 170 subjects were diagnosed with Smith-Lemli-Opitz syndrome soon after birth. RESULTS: All five cases were diagnosed with Smith-Lemli-Opitz syndrome within 6 weeks of life, with no family history of either disorder. All cases had pathologically elevated 7-dehydrocholesterol levels and two of the five cases had previously reported pathogenic 7-dehydrocholesterol reductase mutations. Smith-Lemli-Opitz syndrome severity scores ranged from mild to classical (2-7). Gestational age at birth ranged from 35 to 39 weeks. Four of the cases were male by karyotype. Pulmonary vein stenosis was diagnosed in all cases within 2 months of life, earlier than most published cohorts. All cases progressed to bilateral disease and three cases developed atresia of at least one vein. Despite catheter and surgical interventions, all subjects' pulmonary vein stenosis rapidly recurred and progressed. Three of the subjects died, at 2 months, 3 months, and 11 months. Survival at 16 months after diagnosis was 43%. CONCLUSIONS: Patients with pulmonary vein stenosis who have a suggestive syndromic presentation should be screened for Smith-Lemli-Opitz syndrome with easily obtainable serum sterol tests. Echocardiograms should be obtained in all newly diagnosed patients with Smith-Lemli-Opitz syndrome, with a low threshold for repeating the study if new respiratory symptoms of uncertain etiology arise. Further studies into the pathophysiology of pulmonary vein stenosis should consider the role of cholesterol-based signaling pathways in the promotion of intimal proliferation.
[Mh] Termos MeSH primário: Anormalidades Múltiplas
Síndrome de Smith-Lemli-Opitz/diagnóstico
Estenose de Veia Pulmonar/diagnóstico
[Mh] Termos MeSH secundário: Angiografia
Pré-Escolar
Ecocardiografia
Evolução Fatal
Feminino
Seguimentos
Seres Humanos
Lactente
Recém-Nascido
Masculino
Estudos Retrospectivos
Estenose de Veia Pulmonar/congênito
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1111/chd.12471


  2 / 526 MEDLINE  
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[PMID]:28220990
[Au] Autor:Sharif NF; Korade Z; Porter NA; Harrison FE
[Ad] Endereço:Neuroscience Program, Vanderbilt University, Nashville, TN, USA.
[Ti] Título:Oxidative stress, serotonergic changes and decreased ultrasonic vocalizations in a mouse model of Smith-Lemli-Opitz syndrome.
[So] Source:Genes Brain Behav;16(6):619-626, 2017 Jul.
[Is] ISSN:1601-183X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Smith-Lemli-Opitz syndrome is an inherited monogenic disorder in which mutations to the 7-dehydrocholesterol (7-DHC) reductase (Dhcr7) gene lead to deficits in cholesterol synthesis. As a result, many patients suffer from gross physiological and neurological deficits. The purpose of this study was to identify a potential abnormal behavioral phenotype in a compound mutant mouse model for Smith-Lemli-Opitz disease (Dhcr7 ) to further validate the model and to provide potential targets for future therapeutic interventions. We also sought to identify some of the underlying changes in brain function that may be responsible for behavioral differences among groups. The Dhcr7 compound mutant mice were smaller than their single mutant littermates. Both single and compound heterozygous mice made fewer ultrasonic vocalizations when separated from the dam, which may suggest a communication deficit in these animals. Striking increases of the highly oxidizable 7-DHC were observed in the compound mutant mice. 7-Dehydrocholesterol is the precursor to cholesterol and builds up because of decreased function of the mutated Dhcr7 enzyme. Additionally, several differences were noted in the serotonergic system including increased expression of the serotonin transporter and increased uptake of serotonin by isolated synaptosomes. We propose that changes to the oxidative environment during development can have a significant impact on the development of serotonergic function and that this contributes to behavioral differences observed in the mutant mice.
[Mh] Termos MeSH primário: Estresse Oxidativo
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Serotonina/metabolismo
Síndrome de Smith-Lemli-Opitz/genética
Vocalização Animal
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Encéfalo/fisiopatologia
Desidrocolesteróis/metabolismo
Feminino
Heterozigoto
Masculino
Camundongos
Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
Síndrome de Smith-Lemli-Opitz/metabolismo
Síndrome de Smith-Lemli-Opitz/fisiopatologia
Ondas Ultrassônicas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dehydrocholesterols); 0 (Serotonin Plasma Membrane Transport Proteins); 333DO1RDJY (Serotonin); BK1IU07GKF (7-dehydrocholesterol); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE
[do] DOI:10.1111/gbb.12376


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[PMID]:28166604
[Au] Autor:Lazarin GA; Haque IS; Evans EA; Goldberg JD
[Ad] Endereço:Counsyl, South San Francisco, CA, USA.
[Ti] Título:Smith-Lemli-Opitz syndrome carrier frequency and estimates of in utero mortality rates.
[So] Source:Prenat Diagn;37(4):350-355, 2017 Apr.
[Is] ISSN:1097-0223
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To tabulate individual allele frequencies and total carrier frequency for Smith-Lemli-Opitz syndrome (SLOS) and compare expected versus observed birth incidences. METHODS: A total of 262 399 individuals with no known indication or increased probability of SLOS carrier status, primarily US based, were screened for SLOS mutations as part of an expanded carrier screening panel. Results were retrospectively analyzed to estimate carrier frequencies in multiple ethnic groups. SLOS birth incidences obtained from existing literature were then compared with these data to estimate the effect of SLOS on fetal survival. RESULTS: Smith-Lemli-Opitz syndrome carrier frequency is highest in Ashkenazi Jews (1 in 43) and Northern Europeans (1 in 54). Comparing predicted birth incidence with that observed in published literature suggests that approximately 42% to 88% of affected conceptuses experience prenatal demise. CONCLUSION: Smith-Lemli-Opitz syndrome is relatively frequent in certain populations and, because of its impact on prenatal and postnatal morbidity and mortality, merits consideration for routine screening. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Triagem de Portadores Genéticos
Síndrome de Smith-Lemli-Opitz/diagnóstico
Síndrome de Smith-Lemli-Opitz/genética
Síndrome de Smith-Lemli-Opitz/mortalidade
[Mh] Termos MeSH secundário: Feminino
Mortalidade Fetal
Frequência do Gene
Triagem de Portadores Genéticos/métodos
Testes Genéticos
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Mutação
Polimorfismo de Nucleotídeo Único
Gravidez
Diagnóstico Pré-Natal/métodos
Diagnóstico Pré-Natal/estatística & dados numéricos
Estudos Retrospectivos
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170207
[St] Status:MEDLINE
[do] DOI:10.1002/pd.5018


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[PMID]:28087213
[Au] Autor:Griffiths WJ; Abdel-Khalik J; Yutuc E; Morgan AH; Gilmore I; Hearn T; Wang Y
[Ad] Endereço:Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
[Ti] Título:Cholesterolomics: An update.
[So] Source:Anal Biochem;524:56-67, 2017 May 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cholesterolomics can be regarded as the identification and quantification of cholesterol, its precursors post squalene, and metabolites of cholesterol and of its precursors, in a biological sample. These molecules include 1,25-dihydroxyvitamin D , steroid hormones and bile acids and intermediates in their respective biosynthetic pathways. In this short article we will concentrate our attention on intermediates in bile acid biosynthesis pathways, in particular oxysterols and cholestenoic acids. These molecular classes are implicated in the aetiology of a diverse array of diseases including autoimmune disease, Parkinson's disease, motor neuron disease, breast cancer, the lysosomal storage disease Niemann-Pick type C and the autosomal recessive disorder Smith-Lemli-Opitz syndrome. Mass spectrometry (MS) is the dominant technology for sterol analysis including both gas-chromatography (GC)-MS and liquid chromatography (LC)-MS and more recently matrix-assisted laser desorption/ionisation (MALDI)-MS for tissue imaging studies. Here we will discuss exciting biological findings and recent analytical improvements.
[Mh] Termos MeSH primário: Colesterol/metabolismo
Hormônios Esteroides Gonadais/metabolismo
Vitamina D/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Doenças Autoimunes/metabolismo
Neoplasias da Mama/metabolismo
Doenças do Sistema Nervoso Central/metabolismo
Feminino
Seres Humanos
Masculino
Síndrome de Smith-Lemli-Opitz/metabolismo
Vitamina D/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Gonadal Steroid Hormones); 1406-16-2 (Vitamin D); 66772-14-3 (1,25-dihydroxyvitamin D); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE


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[PMID]:27526097
[Au] Autor:Aslan A; Borcek AO; Pamukcuoglu S; Baykaner MK
[Ad] Endereço:Neurosurgery Department, Faculty of Medicine, Gazi University, Ankara, Turkey. ayferaslan86@gmail.com.
[Ti] Título:Intracranial undifferentiated malign neuroglial tumor in Smith-Lemli-Opitz syndrome: A theory of a possible predisposing factor for primary brain tumors via a case report.
[So] Source:Childs Nerv Syst;33(1):171-177, 2017 Jan.
[Is] ISSN:1433-0350
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Smith-Lemli-Opitz Syndrome (SLOS) is a rare hereditary autosomal recessive disorder with broken cholesterol synthesis causing by 7-dehydrocholesterol reductase deficiency. Although the clinical features and pathogenesis is well-defined, it is unknown whether there is a relationship between SLOS and neoplastic processes, especially brain neoplasms. PURPOSE: We aimed to attract the attentions to any possibility of relation between SLOS and intracranial tumor development via a pediatric case with both intracranial high-grade neuroglial tumor and SLOS, and thus to contribute an additional data to the literature on togetherness of these two clinical conditions. METHOD: In our clinic, we experienced an interesting case of a 10-year-old child with both SLOS and huge brain tumor as rarely seen. Here, we reviewed the features and pathophysiology of SLOS and brain tumors via this case. RESULTS: The patient was operated in our clinic, after, his brain tumor had been diagnosed, and his histopathology was resulted in undifferentiated malignant neuroglial WHO grade 4 tumor. CONCLUSION: According to current literature, our case is the first report on coexisting of SLOS and intracranial undifferentiated malignant neuroglial tumor. Common pathways like impaired sonic hedgehog (Shh) signaling pathway may be considered for pathogenesis of a probable link between SLOS and brain tumors in further studies.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/complicações
Glioma/complicações
Síndrome de Smith-Lemli-Opitz
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/análise
Neoplasias Encefálicas/patologia
Criança
Evolução Fatal
Glioma/patologia
Seres Humanos
Imuno-Histoquímica
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160816
[St] Status:MEDLINE
[do] DOI:10.1007/s00381-016-3214-z


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[PMID]:27520299
[Au] Autor:Prabhu AV; Luu W; Sharpe LJ; Brown AJ
[Ad] Endereço:School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
[Ti] Título:Phosphorylation regulates activity of 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme of cholesterol synthesis.
[So] Source:J Steroid Biochem Mol Biol;165(Pt B):363-368, 2017 Jan.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cholesterol is essential for survival, but too much or too little can cause disease. Thus, cholesterol levels must be kept within close margins. 7-dehydrocholesterol reductase (DHCR7) is a terminal enzyme of cholesterol synthesis, and is essential for embryonic development. Largely, DHCR7 research is associated with the developmental disease Smith-Lemli-Opitz syndrome, which is caused by mutations in the DHCR7 gene. However, little is known about what regulates DHCR7 activity. Here we provide evidence that phosphorylation plays a role in controlling DHCR7 activity, which may provide a means to divert flux from cholesterol synthesis to vitamin D production. DHCR7 activity was significantly decreased when we used pharmacological inhibitors against two important kinases, AMP-activated protein kinase and protein kinase A. Moreover, mutating a known phosphorylated residue, S14, also decreased DHCR7 activity. Thus, we demonstrate that phosphorylation modulates DHCR7 activity in cells, and contributes to the overall synthesis of cholesterol, and probably vitamin D.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/metabolismo
Colesterol/biossíntese
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
Regulação Enzimológica da Expressão Gênica
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetinae
Cricetulus
Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Mutagênese Sítio-Dirigida
Mutação
Fosforilação
RNA Interferente Pequeno/metabolismo
Síndrome de Smith-Lemli-Opitz/metabolismo
Vitamina D/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Interfering); 1406-16-2 (Vitamin D); 97C5T2UQ7J (Cholesterol); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160814
[St] Status:MEDLINE


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[PMID]:26976653
[Au] Autor:Griffiths WJ; Abdel-Khalik J; Crick PJ; Ogundare M; Shackleton CH; Tuschl K; Kwok MK; Bigger BW; Morris AA; Honda A; Xu L; Porter NA; Björkhem I; Clayton PT; Wang Y
[Ad] Endereço:College of Medicine, Grove Building, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: w.j.griffiths@swansea.ac.uk.
[Ti] Título:Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients.
[So] Source:J Steroid Biochem Mol Biol;169:77-87, 2017 May.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ -sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-dehydrocholesterol, 3ß,5α-dihydroxycholest-7-en-6-one and 7α,8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5ng/mL).
[Mh] Termos MeSH primário: Oxisteróis/sangue
Síndrome de Smith-Lemli-Opitz/sangue
Esteróis/sangue
[Mh] Termos MeSH secundário: Colestadienóis/sangue
Desidrocolesteróis/sangue
Radicais Livres/química
Seres Humanos
Mutação
Oxirredutases atuantes sobre Doadores de Grupo CH-CH
Plasma/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestadienols); 0 (Dehydrocholesterols); 0 (Free Radicals); 0 (Oxysterols); 0 (Sterols); 70741-38-7 (cholesta-5,8-dien-3 beta-ol); BK1IU07GKF (7-dehydrocholesterol); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160316
[St] Status:MEDLINE


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[PMID]:27697512
[Au] Autor:Prabhu AV; Luu W; Li D; Sharpe LJ; Brown AJ
[Ad] Endereço:School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia.
[Ti] Título:DHCR7: A vital enzyme switch between cholesterol and vitamin D production.
[So] Source:Prog Lipid Res;64:138-151, 2016 10.
[Is] ISSN:1873-2194
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The conversion of 7-dehydrocholesterol to cholesterol, the final step of cholesterol synthesis in the Kandutsch-Russell pathway, is catalyzed by the enzyme 7-dehydrocholesterol reductase (DHCR7). Homozygous or compound heterozygous mutations in DHCR7 lead to the developmental disease Smith-Lemli-Opitz syndrome, which can also result in fetal mortality, highlighting the importance of this enzyme in human development and survival. Besides serving as a substrate for DHCR7, 7-dehydrocholesterol is also a precursor of vitamin D via the action of ultraviolet light on the skin. Thus, DHCR7 exerts complex biological effects, involved in both cholesterol and vitamin D production. Indeed, we argue that DHCR7 can act as a switch between cholesterol and vitamin D synthesis. This review summarizes current knowledge about the critical enzyme DHCR7, highlighting recent findings regarding its structure, transcriptional and post-transcriptional regulation, and its links to vitamin D synthesis. Greater understanding about DHCR7 function, regulation and its place within cellular metabolism will provide important insights into its biological roles.
[Mh] Termos MeSH primário: Colesterol/metabolismo
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Vitamina D/metabolismo
[Mh] Termos MeSH secundário: Animais
Desidrocolesteróis/metabolismo
Embrião não Mamífero/metabolismo
Seres Humanos
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Domínios Proteicos
Síndrome de Smith-Lemli-Opitz/metabolismo
Síndrome de Smith-Lemli-Opitz/patologia
Xenopus/crescimento & desenvolvimento
Xenopus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Dehydrocholesterols); 1406-16-2 (Vitamin D); 97C5T2UQ7J (Cholesterol); BK1IU07GKF (7-dehydrocholesterol); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161005
[St] Status:MEDLINE


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[PMID]:27401223
[Au] Autor:Boland MR; Tatonetti NP
[Ad] Endereço:Department of Biomedical Informatics, Columbia University, New York, NY, USA.
[Ti] Título:Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review.
[So] Source:Pharmacogenomics J;16(5):411-29, 2016 Oct.
[Is] ISSN:1473-1150
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mendelian diseases contain important biological information regarding developmental effects of gene mutations that can guide drug discovery and toxicity efforts. In this review, we focus on Smith-Lemli-Opitz syndrome (SLOS), a rare Mendelian disease characterized by compound heterozygous mutations in 7-dehydrocholesterol reductase (DHCR7) resulting in severe fetal deformities. We present a compilation of SLOS-inducing DHCR7 mutations and the geographic distribution of those mutations in healthy and diseased populations. We observed that several mutations thought to be disease causing occur in healthy populations, indicating an incomplete understanding of the condition and highlighting new research opportunities. We describe the functional environment around DHCR7, including pharmacological DHCR7 inhibitors and cholesterol and vitamin D synthesis. Using PubMed, we investigated the fetal outcomes following prenatal exposure to DHCR7 modulators. First-trimester exposure to DHCR7 inhibitors resulted in outcomes similar to those of known teratogens (50 vs 48% born-healthy). DHCR7 activity should be considered during drug development and prenatal toxicity assessment.
[Mh] Termos MeSH primário: Anormalidades Induzidas por Medicamentos/genética
Inibidores Enzimáticos/efeitos adversos
Exposição Materna/efeitos adversos
Mutação
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética
Farmacogenética
Síndrome de Smith-Lemli-Opitz/genética
[Mh] Termos MeSH secundário: Anormalidades Induzidas por Medicamentos/enzimologia
Anormalidades Induzidas por Medicamentos/epidemiologia
Animais
Colesterol/metabolismo
Evolução Molecular
Feminino
Frequência do Gene
Deriva Genética
Predisposição Genética para Doença
Hereditariedade
Seres Humanos
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Fenótipo
Gravidez
Medição de Risco
Fatores de Risco
Síndrome de Smith-Lemli-Opitz/tratamento farmacológico
Síndrome de Smith-Lemli-Opitz/enzimologia
Síndrome de Smith-Lemli-Opitz/epidemiologia
Vitamina D/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 1406-16-2 (Vitamin D); 97C5T2UQ7J (Cholesterol); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.21 (7-dehydrocholesterol reductase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160713
[St] Status:MEDLINE
[do] DOI:10.1038/tpj.2016.48


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[PMID]:27315086
[Au] Autor:Balajthy A; Somodi S; Petho Z; Péter M; Varga Z; Szabó GP; Paragh G; Vígh L; Panyi G; Hajdu P
[Ad] Endereço:Department of Biophysics and Cell Biology, Faculty of General Medicine, University of Debrecen, Egyetem tér 1., Debrecen, 4032, Hungary.
[Ti] Título:7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome.
[So] Source:Pflugers Arch;468(8):1403-18, 2016 Aug.
[Is] ISSN:1432-2013
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In vitro manipulation of membrane sterol level affects the regulation of ion channels and consequently certain cellular functions; however, a comprehensive study that confirms the pathophysiological significance of these results is missing. The malfunction of 7-dehydrocholesterol (7DHC) reductase in Smith-Lemli-Opitz syndrome (SLOS) leads to the elevation of the 7-dehydrocholesterol level in the plasma membrane. T lymphocytes were isolated from SLOS patients to assess the effect of the in vivo altered membrane sterol composition on the operation of the voltage-gated Kv1.3 channel and the ion channel-dependent mitogenic responses. We found that the kinetic and equilibrium parameters of Kv1.3 activation changed in SLOS cells. Identical changes in Kv1.3 operation were observed when control/healthy T cells were loaded with 7DHC. Removal of the putative sterol binding sites on Kv1.3 resulted in a phenotype that was not influenced by the elevation in membrane sterol level. Functional assays exhibited impaired activation and proliferation rate of T cells probably partially due to the modified Kv1.3 operation. We concluded that the altered membrane sterol composition hindered the operation of Kv1.3 as well as the ion channel-controlled T cell functions.
[Mh] Termos MeSH primário: Canal de Potássio Kv1.3/metabolismo
Síndrome de Smith-Lemli-Opitz/metabolismo
Linfócitos T/efeitos dos fármacos
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Criança
Desidrocolesteróis/metabolismo
Seres Humanos
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dehydrocholesterols); 0 (Kv1.3 Potassium Channel); BK1IU07GKF (7-dehydrocholesterol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160618
[St] Status:MEDLINE
[do] DOI:10.1007/s00424-016-1851-4



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