Molecular Diagnosis & Therapy最新文献_第8页

Molecular Dynamic Simulations to Determine Individualized Therapy: Tetrabenazine for the GNAO1 Encephalopathy E246K Variant 通过分子动力学模拟确定个性化疗法：四苯嗪治疗 GNAO1 脑病 E246K 变体

IF 4 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-04-06 DOI: 10.1007/s40291-024-00706-0

{"title":"Molecular Dynamic Simulations to Determine Individualized Therapy: Tetrabenazine for the GNAO1 Encephalopathy E246K Variant","authors":"","doi":"10.1007/s40291-024-00706-0","DOIUrl":"https://doi.org/10.1007/s40291-024-00706-0","url":null,"abstract":"<h3>Abstract</h3> <h3>Introduction</h3> GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. <h3>Methods</h3> Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. <h3>Results and discussion</h3> We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease. ","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"298 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic Approaches to Investigate JAK2-Unmutated Erythrocytosis Based on a Single Tertiary Center Experience 基于单个三级中心经验的 JAK2-未突变红细胞增多症诊断调查方法

IF 4 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-04-03 DOI: 10.1007/s40291-024-00703-3

Youngeun Lee, Soo Hyun Seo, Jinho Kim, Sang-A Kim, Ji Yun Lee, Jeong-Ok Lee, Soo-Mee Bang, Kyoung Un Park, Sang Mee Hwang

{"title":"Diagnostic Approaches to Investigate JAK2-Unmutated Erythrocytosis Based on a Single Tertiary Center Experience","authors":"Youngeun Lee, Soo Hyun Seo, Jinho Kim, Sang-A Kim, Ji Yun Lee, Jeong-Ok Lee, Soo-Mee Bang, Kyoung Un Park, Sang Mee Hwang","doi":"10.1007/s40291-024-00703-3","DOIUrl":"https://doi.org/10.1007/s40291-024-00703-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3>Erythrocytosis is attributed to various clinical and molecular factors. Many cases of JAK2-unmutated erythrocytosis remain undiagnosed. We investigated the characteristics and causes of JAK2-unmutated erythrocytosis.<h3 data-test=\"abstract-sub-heading\">Methods</h3>We assessed the clinical and laboratory results of patients with erythrocytosis without JAK2 mutations and performed targeted next-generation sequencing (NGS) panels for somatic and germline mutations.<h3 data-test=\"abstract-sub-heading\">Results</h3>In total, 117 patients with JAK2-unmutated erythrocytosis were included. The median hemoglobin and hematocrit levels were 17.9 g/dL and 53.4%, respectively. Erythropoietin levels were not below the reference range. Thrombotic events were reported in 17 patients (14.5%). Among JAK2-unmutated patients, 44 had undergone targeted panel sequencing consisting of myeloid neoplasm-related genes, and 16 had one or more reportable variants in ASXL1 (5/44), TET2, CALR, FLT3, and SH2B3 (2/44). Additional testing for germline causes revealed eight variants in seven genes in eight patients, including NF1, BPGM, EPAS1, PIEZO1, RHAG, SH2B3, and VHL genes. One NF1 pathogenic, one BPGM likely pathogenic, and six variants of undetermined significance were detected.<h3 data-test=\"abstract-sub-heading\">Conclusion</h3>Somatic and germline mutations were identified in 36.4% and 33.3 % of the JAK2-unmutated group; most variants had unknown clinical significance. Not all genetic causes have been identified; comprehensive diagnostic approaches are crucial for identifying the cause of erythrocytosis.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Personalizing Oncolytic Immunovirotherapy Approaches. 肿瘤溶解免疫疗法的个性化应用

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2023-12-27 DOI: 10.1007/s40291-023-00689-4

Georgios M Stergiopoulos, Ianko Iankov, Evanthia Galanis

{"title":"Personalizing Oncolytic Immunovirotherapy Approaches.","authors":"Georgios M Stergiopoulos, Ianko Iankov, Evanthia Galanis","doi":"10.1007/s40291-023-00689-4","DOIUrl":"10.1007/s40291-023-00689-4","url":null,"abstract":"Development of successful cancer therapeutics requires exploration of the differences in genetics, metabolism, and interactions with the immune system among malignant and normal cells. The clinical observation of spontaneous tumor regression following natural infection with microorganism has created the premise of their use as cancer therapeutics. Oncolytic viruses (OVs) originate from viruses with attenuated virulence in humans, well-characterized vaccine strains of known human pathogens, or engineered replication-deficient viral vectors. Their selectivity is based on receptor expression level and post entry restriction factors that favor replication in the tumor, while keeping the normal cells unharmed. Clinical trials have demonstrated a wide range of patient responses to virotherapy, with subgroups of patients significantly benefiting from OV administration. Tumor-specific gene signatures, including antiviral interferon-stimulated gene (ISG) expression profile, have demonstrated a strong correlation with tumor permissiveness to infection. Furthermore, the combination of OVs with immunotherapeutics, including anticancer vaccines and immune checkpoint inhibitors [ICIs, such as anti-PD-1/PD-L1 or anti-CTLA-4 and chimeric antigen receptor (CAR)-T or CAR-NK cells], could synergistically improve the therapeutic outcome. Creating response prediction algorithms represents an important step for the transition to individualized immunovirotherapy approaches in the clinic. Integrative predictors could include tumor mutational burden (TMB), inflammatory gene signature, phenotype of tumor-infiltrating lymphocytes, tumor microenvironment (TME), and immune checkpoint receptor expression on both immune and target cells. Additionally, the gut microbiota has recently been recognized as a systemic immunomodulatory factor and could further be used in the optimization of individualized immunovirotherapy algorithms.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"153-168"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exagamglogene Autotemcel: First Approval. Exagamglogene Autotemcel：首次批准。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2024-01-17 DOI: 10.1007/s40291-024-00696-z

Sheridan M Hoy

{"title":"Exagamglogene Autotemcel: First Approval.","authors":"Sheridan M Hoy","doi":"10.1007/s40291-024-00696-z","DOIUrl":"10.1007/s40291-024-00696-z","url":null,"abstract":"Exagamglogene autotemcel (Casgevy™) is a genetically modified autologous CD34+ cell enriched population. It contains human haematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 (a DNA double strand break-inducing nuclease system) to differentiate into erythroid cells that produce high levels of foetal hemoglobin. Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, exagamglogene autotemcel received its first approval on 16 November 2023 in the UK for the treatment of transfusion-dependent β-thalassemia (TDT) in patients aged ≥ 12 years for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen matched related HSC donor is not available. On the same day, it was also approved in the UK for the treatment of sickle cell disease (SCD) in patients aged ≥ 12 years with recurrent vasoocclusive crises (VOCs) who have the βS/βS, βS/β+ or βS/β0 genotype for whom HSC transplantation is appropriate and a human leukocyte antigen matched related HSC donor is not available. Subsequently, exagamglogene autotemcel was approved in the USA on 8 December 2023 for the treatment of SCD in patients aged ≥ 12 years with recurrent VOCs and received a positive opinion in the EU on 14 December 2023 for the treatment of TDT and SCD. A regulatory assessment of exagamglogene autotemcel is currently underway for the treatment of TDT in the USA. This article summarizes the milestones in the development of exagamglogene autotemcel leading to these first approvals.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"133-139"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Complement System and C4b-Binding Protein: A Focus on the Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance. 补体系统与 C4b 结合蛋白：聚焦 C4BPα 作为生物标记物预测氯吡格雷耐药性的前景。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2024-01-23 DOI: 10.1007/s40291-023-00691-w

Hong-Guang Xie, Li-Ping Jiang, Ting Tai, Jin-Zi Ji, Qiong-Yu Mi

{"title":"The Complement System and C4b-Binding Protein: A Focus on the Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance.","authors":"Hong-Guang Xie, Li-Ping Jiang, Ting Tai, Jin-Zi Ji, Qiong-Yu Mi","doi":"10.1007/s40291-023-00691-w","DOIUrl":"10.1007/s40291-023-00691-w","url":null,"abstract":"The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b-binding protein (C4BP) was the first circulating complement regulatory protein identified and it functions as an important complement inhibitor. C4BP can suppress the over-activation of complement components and prevent the complement system from attacking the host cells through the binding of complement cleavage products C4b and C3b, working in concert as a cofactor for factor I in the degradation of C4b and C3b, and consequently preventing or reducing the assembly of C3 convertase and C5 convertase, respectively. C4BP, particularly C4BP α-chain (C4BPα), exerts its unique inhibitory effects on complement activation and opsonization, systemic inflammation, and platelet activation and aggregation. It has long been acknowledged that crosstalk or interplay exists between the complement system and platelets. Our unpublished preliminary data suggest that circulating C4BPα exerts its antiplatelet effects through inhibition of both complement activity levels and complement-induced platelet reactivity. Plasma C4BPα levels appear to be significantly higher in patients sensitive to, rather than resistant to, clopidogrel, and we suggest that a plasma C4BPα measurement could be used to predict clopidogrel resistance in the clinical settings.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"189-199"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute Fluid Biomarkers for Diagnosis and Prognosis in Children with Mild Traumatic Brain Injury: A Systematic Review. 用于轻度脑外伤儿童诊断和预后的急性体液生物标志物：系统回顾。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2023-12-22 DOI: 10.1007/s40291-023-00685-8

Armaan K Malhotra, Kentaro Ide, Zaid Salaheen, Quenby Mahood, Jessie Cunningham, Jamie Hutchison, Anne-Marie Guerguerian

{"title":"Acute Fluid Biomarkers for Diagnosis and Prognosis in Children with Mild Traumatic Brain Injury: A Systematic Review.","authors":"Armaan K Malhotra, Kentaro Ide, Zaid Salaheen, Quenby Mahood, Jessie Cunningham, Jamie Hutchison, Anne-Marie Guerguerian","doi":"10.1007/s40291-023-00685-8","DOIUrl":"10.1007/s40291-023-00685-8","url":null,"abstract":"Background and objective: Fluid biomarkers have the potential to improve the accuracy of diagnosis and prognosis in children with mild traumatic brain injury. Our primary objective was to assess the diagnostic and prognostic utility of acute blood and fluid biomarkers in children with mild traumatic brain injury.Methods: We performed a systematic review of the published literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Fluid biomarker studies assessing pediatric mild traumatic brain injury diagnosis or prognosis were included if blood or fluids were sampled within 24 h of injury.Results: Thirty-two studies involving 4743 patients were included comprising 25 diagnostic studies and ten prognostic studies with three studies assessing both diagnosis and prognosis. Sixteen of the 25 diagnostic studies reported the area under the receiver operating characteristic curve (AUC) for predicting abnormal computed tomography scans of the head; S100 calcium binding protein B (S100B, N = 6 studies, AUC range 0.67-1.00), glial fibrillary acidic protein (N = 5, AUC range 0.41-0.85), ubiquitin C-terminal hydrolase (N = 3, AUC 0.59 and 0.83), neuron specific enolase (N = 1, AUC 0.99), total tau (N = 1, AUC 0.65), and interleukin-6 (N = 1, AUC 0.61). In four of the ten prognostic studies, increased acute serum S100B levels, tumor necrosis factor-α, or interleukin-8 were associated with post-concussive symptoms or fatigue from 3 to 12 months post-injury.Conclusions: The largest amount of evidence supported the potential use of S100B, glial fibrillary acidic protein, and UCH-L1, but there was mixed accuracy for diagnosis and prognostication for all biomarkers in pediatric mTBI.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"169-187"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comment on "Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta‑Analysis". 关于 "乳腺癌中人类白细胞抗原 I 类表达的预后和临床意义：元分析 "发表评论。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2024-02-20 DOI: 10.1007/s40291-024-00700-6

Wei Han, Li-Zhou Shi, Yu-Wei Zhang, Hao-Nan Wang

引用次数: 0

Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances. 从当前的免疫肿瘤基因组学进展中揭示新兴的肛门癌临床生物标记。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2024-01-24 DOI: 10.1007/s40291-023-00692-9

Soledad Iseas, Golubicki Mariano, Louis Gros, Nabil Baba-Hamed, Vincent De Parades, Julien Adam, Eric Raymond, Martin Carlos Abba

{"title":"Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.","authors":"Soledad Iseas, Golubicki Mariano, Louis Gros, Nabil Baba-Hamed, Vincent De Parades, Julien Adam, Eric Raymond, Martin Carlos Abba","doi":"10.1007/s40291-023-00692-9","DOIUrl":"10.1007/s40291-023-00692-9","url":null,"abstract":"Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in \"omics\" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"201-214"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADORA3: A Key Player in the Pathogenesis of Intracranial Aneurysms and a Potential Diagnostic Biomarker. ADORA3：颅内动脉瘤发病机制的关键参与者和潜在的诊断生物标志物。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2024-02-11 DOI: 10.1007/s40291-024-00694-1

Rui-Ting Hu, Hao-Wei Deng, Wen-Bin Teng, Shao-Dan Zhou, Zi-Ming Ye, Zi-Mei Dong, Chao Qin

{"title":"ADORA3: A Key Player in the Pathogenesis of Intracranial Aneurysms and a Potential Diagnostic Biomarker.","authors":"Rui-Ting Hu, Hao-Wei Deng, Wen-Bin Teng, Shao-Dan Zhou, Zi-Ming Ye, Zi-Mei Dong, Chao Qin","doi":"10.1007/s40291-024-00694-1","DOIUrl":"10.1007/s40291-024-00694-1","url":null,"abstract":"Background: The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection.Methods: IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples.Results: Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of \"limma\" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83.Conclusions: High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"225-235"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chimeric Genes Causing 11β-Hydroxylase Deficiency: Implications in Clinical and Molecular Diagnosis. 导致 11β 羟化酶缺陷的嵌合基因：临床和分子诊断的意义。

IF 4.1 3区医学

Molecular Diagnosis & Therapy Pub Date : 2024-03-01 Epub Date: 2024-02-07 DOI: 10.1007/s40291-024-00697-y

Paola Concolino

{"title":"Chimeric Genes Causing 11β-Hydroxylase Deficiency: Implications in Clinical and Molecular Diagnosis.","authors":"Paola Concolino","doi":"10.1007/s40291-024-00697-y","DOIUrl":"10.1007/s40291-024-00697-y","url":null,"abstract":"Deficiency of 11β-hydroxylase (11β-OHD) is the second most common cause of congenital adrenal hyperplasia (CAH), accounting for 0.2-8% of all cases. The disease is transmitted as an autosomal recessive trait and the underlying genetic causes of 11β-OHD are primarily small pathogenic variants affecting the CYP11B1 gene coding the 11β-hydroxylase enzyme. However, special events complicate the molecular diagnosis of 11β-OHD such as an unequal crossing over between the CYP11B2 (coding aldosterone synthase enzyme) and CYP11B1 genes. The resulting allele contains a hybrid gene, with a CYP11B2 5'-end and a CYP11B1 3'-end, where the CYP11B1 gene is under the control of the CYP11B2 promoter and thus not responding to the adrenocorticotropin (ACTH) but to angiotensin II and K+. This leads a reduction of cortisol production in 11β-OHD. In particular, CYP11B2/CYP11B1 chimeric genes can be distinguished into two groups depending on the breakpoint site: chimeras with breakpoint after the exon 5 of CYP11B2 preserve the aldosterone synthase activity, the others with breakpoint before exon 5 lose this function. In the last case, a more severe phenotype is expected. The aim of this review was to explore the setting of CYP11B2/CYP11B1 chimeras in 11β-OHD, performing a careful review of clinical literature cases.","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"215-224"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0