预约演示

更新于：2025-05-07

Lathosterolosis

烷醇症

更新于：2025-05-07

基本信息

别名

3-beta-hydroxysteroid-delta(5)-desaturase deficiency、Deficiency of 3-beta-hydroxysteroid-delta(5)-desaturase、LATHOS

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简介

An extremely rare inborn error of sterol biosynthesis with manifestations of facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease. Only 4 cases have been reported in the literature to date. Lathosterolosis is due to mutations in the SC5D gene (11q23.3). A mutation in this gene leads to a deficiency in 3-beta-hydroxysteroid-delta-5-desaturase, which is necessary in the conversion of lathosterol into 7-dehydrocholesterol. This prevents the synthesis of cholesterol, which among other functions acts as a structural lipid, a precursor for bile acids and steroid hormones, and is necessary for the maturation of hedgehog morphogens during embryonic development. Inherited in an autosomal recessive manner.

关联

项与烷醇症相关的临床试验

NCT05047354

/ RecruitingN/AIIT

Natural History Investigation Into Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism

Background:
Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder. It can cause birth defects and developmental delays. There is no cure for SLOS or other inherited diseases related to cholesterol production or storage. The data gained in this study may help researchers find ways to measure how well future treatments work.
Objective:
To learn more about SLOS and related disorders and how these diseases affect participants and relatives.
Eligibility:
People of any age who have or are suspected to have SLOS or another inherited disease related to cholesterol production or storage. Relatives are also needed.
Design:
Participants will be screened with a medical record review.
Participants will have visits every 6 to 12 months. They will have a physical exam. They will fill out a survey about their medical and behavioral history. They may have an eye exam. They may have a neurodevelopmental assessment. They may have a hearing test. Their outer and middle ears may be examined. Their ability to speak, understand speech, eat, and swallow may be assessed. They may get X-rays while they chew and swallow. Their functional ability and needs for adaptive devices or braces may be assessed. They may have a lumbar puncture. Photographs may be taken of their face and body.
Participants who cannot visit the NIH and relatives will have a virtual visit once a year. They will talk about their medical history and symptoms. They give blood, urine, and skin samples at a lab near their home. They will fill out a survey about their medical and behavioral history.
Participation will last for several years.

开始日期2021-06-23

申办/合作机构

National Institute of Child Health & Human Development

100 项与烷醇症相关的临床结果

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100 项与烷醇症相关的转化医学

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0 项与烷醇症相关的专利（医药）

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108

项与烷醇症相关的文献（医药）

2025-01-01·Stem Cell Reviews and Reports

The Different Responsiveness of C3- and C5-deficient Murine BM Cells to Oxidative Stress Explains Why C3 Deficiency, in Contrast to C5 Deficiency, Correlates with Better Pharmacological Mobilization and Engraftment of Hematopoietic Cells

Article

作者: Ratajczak, Mariusz Z. ; Ratajczak, Mariusz Z ; Konopko, Adrian ; Kucia, Magdalena ; Łukomska, Agnieszka

AbstractThe liver-derived circulating in peripheral blood and intrinsic cell-expressed complement known as complosome orchestrate the trafficking of hematopoietic stem/progenitor cells (HSPCs) both during pharmacological mobilization and homing/engraftment after transplantation. Our previous research demonstrated that C3 deficient mice are easy mobilizers, and their HSPCs engraft properly in normal mice. In contrast, C5 deficiency correlates with poor mobilization and defects in HSPCs’ homing and engraftment. The trafficking of HSPCs during mobilization and homing/engraftment follows the sterile inflammation cues in the BM microenvironment caused by stress induced by pro-mobilizing drugs or myeloablative conditioning for transplantation. Therefore, to explain deficiencies in HSPC trafficking between C3-KO and C5-KO mice, we evaluated the responsiveness of C3 and C5 deficient cells to low oxidative stress. As reported, oxidative stress in BM is mediated by the activation of purinergic signaling, which is triggered by the elevated level of extracellular adenosine triphosphate (eATP) and by the activation of the complement cascade (ComC). In the current work, we noticed that BM lineage negative cells (lin−) isolated from C3-KO mice display several mitochondrial defects reflected by an impaired ability to adapt to oxidative stress. In contrast, C5-KO-derived BM cells show a high level of adaptation to this challenge. To support this data, C3-KO BM lin− cells were highly responsive to eATP stimulation, which correlates with enhanced levels of reactive oxygen species (ROS) generation and more efficient activation of intracellular Nlrp3 inflammasome. We conclude that the enhanced sensitivity of C3-KO mice cells to oxidative stress and better activation of the Nox2-ROS-Nlrp3 inflammasome signaling axis explains the molecular level differences in trafficking between C3- and C5-deficient HSPCs.Graphical Abstract

2024-04-01·European Journal of Immunology

Fcgr2b and Fcgr3 are the major genetic factors for cartilage antibody‐induced arthritis, overriding the effect of Hc encoding complement C5

Article

作者: Holmdahl, Rikard ; Zhao, Danxia ; Xu, Bingze ; Pandey, Rajan Kumar ; Lundström, Susanna L ; Xu, Zhongwei ; Moreno-Giró, Àlex ; Krämer, Alexander

AbstractLike rheumatoid arthritis (RA) in humans, collagen‐induced arthritis (CIA) in mice is associated with not only MHC class II genetic polymorphism but also, to some extent, with other loci including genes encoding Fc gamma receptors (FCGRs) and complement C5. In this study, we used a cartilage antibody‐induced arthritis (CAIA) model in which arthritis develops within a 12‐h timeframe, to determine the relative importance of FCGRs and C5 (Hc). In CAIA, inhibiting or deleting FCGR3 substantially hindered arthritis development, underscoring the crucial role of this receptor. Blocking FCGR3 also reduced the levels of FCGR4, and vice versa. When employing an IgG1 arthritogenic cocktail that exclusively interacts with FCGR2B and FCGR3, joint inflammation was promptly initiated in Fcgr2b−− mice but not in Fcgr3−− mice, suggesting that FCGR3 is sufficient for CAIA development. Regarding complement activation, Fcgr2b++.Hc** mice with C5 mutated were fully resistant to CAIA, whereas Fcgr2b−−.Hc** mice developed arthritis rapidly. We conclude that FCGR3 is essential and sufficient for CAIA development, particularly when induced by IgG1 antibodies. The human ortholog of mouse FCGR3, FCGR2A, may be associated with RA pathogenesis. FCGR2B deficiency allows for rapid arthritis progression and overrides the resistance conferred by C5 deficiency.

2023-01-01·Neurotrauma reports

Complement Component 5 (C5) Deficiency Improves Cognitive Outcome After Traumatic Brain Injury and Enhances Treatment Effects of Complement Inhibitors C1-Inh and CR2-Crry in a Mouse Model.

Article

作者: Reutens, David ; Chen, Min ; Tomlinson, Stephen ; Maskey, Dhiraj ; Woodruff, Trent M ; Edwards, Stephen R

A potent effector of innate immunity, the complement system contributes significantly to the pathophysiology of traumatic brain injury (TBI). This study investigated the role of the complement cascade in neurobehavioral outcomes and neuropathology after TBI. Agents acting at different levels of the complement system, including 1) C1 esterase inhibitor (C1-Inh), 2) CR2-Crry, an inhibitor of all pathways acting at C3, and 3) the selective C5aR1 antagonist, PMX205, were administered at 1 h post-TBI. Their effects were evaluated on motor function using the rotarod apparatus, cognitive function using the active place avoidance (APA) task, and brain lesion size at a chronic stage after controlled cortical impact injury in C5-sufficient (C5^+/+) and C5-deficient (C5^-/-) CD1 mice. In post-TBI C5^+/+ mice, rotarod performance was improved by CR2-Crry, APA performance was improved by CR2-Crry and PMX205, and brain lesion size was reduced by PMX205. After TBI, C5^-/- mice performed better in the APA task compared with C5^+/+ mice. C5 deficiency enhanced the effect of C1-Inh on motor function and brain damage and the effect of CR2-Crry on brain damage after TBI. Our findings support critical roles for C3 in motor deficits, the C3/C5/C5aR1 axis in cognitive deficits, and C5aR1 signaling in brain damage after TBI. Findings suggest the combination of C5 inhibition with C1-Inh and CR2-Crry as potential therapeutic strategies in TBI.

项与烷醇症相关的新闻（医药）

2022-06-15

·生物谷

Nucleic Acids Research:浙江大学农学院马忠华团队合作发文揭示赤霉病菌适应小麦高铁环境的表观调控新机制

揭示了转录因子FgPacC介导小麦赤霉病菌适应寄主高铁环境的表观遗传新机制，研究结果有助于深入理解病原菌寄主适应性的分子机制，并为赤霉病防控新策略的制定提供理论基础。浙江大学农学院马忠华团队与南京农业大学植物保护学院高学文团队合作在《 Nucleic Acids Research》上发表题为“Inhibition of histone acetyltransferase GCN5 by atranscription factor FgPacC controls fungal adaptionto host-derived iron stress”的研究论文，揭示了转录因子FgPacC介导小麦赤霉病菌适应寄主高铁环境的表观遗传新机制，研究结果有助于深入理解病原菌寄主适应性的分子机制，并为赤霉病防控新策略的制定提供理论基础。铁（Iron）作为一种生命必需的基本元素，在生物体的呼吸、DNA 合成和修复、核糖体合成等代谢过程中发挥了重要作用，但细胞内积累过量的铁离子会引起 Fenton 反应的发生，进而导致活性氧的积累对细胞产生毒害。因此病原菌侵染宿主过程中进化出复杂的策略精细调节铁的获取、消耗和储存，从而维持细胞内铁的稳态。在哺乳动物和禾本科植物中均发现，寄主可在病菌侵染位点大量积累铁离子从而抑制病菌的侵染，但病菌如何适应宿主的高铁环境目前尚不清楚。近年来，由于气候变化、大面积小麦/玉米轮作和秸秆还田等因素的影响，赤霉病在我国呈加重发生态势，严重影响小麦产量和品质。在该研究中，作者发现赤霉病菌-小麦互作过程中，小麦质外体中积累大量的铁离子（Fe2+）进而抑制赤霉病的侵染。为克服这种胁迫，赤霉病菌通过诱导植物碱化，使得转录因子FgPacC被切割成30-kDa的活性形式（FgPacC30）并易位到细胞核中，FgPacC30直接与真菌铁吸收基因的启动子结合并抑制其表达。有意思的是，作者首次发现FgPacC30能够结合并抑制组蛋白乙酰转移酶FgGcn5活性，进而抑制的H3K18和H2BK11乙酰化水平，阻断铁吸收基因的表达。此外，作者还鉴定到蛋白激酶FgHal4，它在高铁条件下参与FgPacC30的磷酸化，从而保护FgPacC30免受26S蛋白酶体依赖性降解。综上所述，转录因子FgPacC通过抑制SAGA（SPT-Ada-Gcn5乙酰转移酶）复合体活性负调控铁吸收基因表达，保护真菌免受寄主高铁胁迫，在表观遗传水平上揭示了病原真菌抵御宿主铁胁迫的分子机制。顾沁副教授和王玉洁博士为论文共同第一作者，顾沁副教授、高学文教授和马忠华教授为共同通讯作者，陈云教授、伍辉军副教授、淮阴师范大学生命科学学院罗玉明教授和威斯康星大学麦迪逊分校Nancy P. Keller教授等也参与了本研究工作，该研究得到国家重点研发计划战略性合作项目、江苏省优秀青年自然科学基金、国家自然科学基金和现代农业产业技术体系的支持。

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