Journal of translational genetics and genomics最新文献

Duchenne muscular dystrophy: diagnosis and perspective of treatment 杜兴氏肌肉萎缩症：诊断与治疗展望

Journal of translational genetics and genomics Pub Date : 2024-07-16 DOI: 10.20517/jtgg.2024.29

Corrado Angelini

引用次数: 0

Challenges in determining the malignant potential of atypical neurofibromas (aNF) using histopathologic features and the potential need for CDKN2A/2B testing: a case report 利用组织病理学特征确定非典型神经纤维瘤（aNF）恶性可能性的挑战以及对 CDKN2A/2B 检测的潜在需求：一份病例报告

Journal of translational genetics and genomics Pub Date : 2024-04-22 DOI: 10.20517/jtgg.2024.02

A. Gross, Sana Z. Mahmood, E. Dombi, Markku M. Miettinen, Mark Raffeld, Anne Dufek, Sneh Patel, Prashant Chittiboina, Brigitte C. Widemann

{"title":"Challenges in determining the malignant potential of atypical neurofibromas (aNF) using histopathologic features and the potential need for CDKN2A/2B testing: a case report","authors":"A. Gross, Sana Z. Mahmood, E. Dombi, Markku M. Miettinen, Mark Raffeld, Anne Dufek, Sneh Patel, Prashant Chittiboina, Brigitte C. Widemann","doi":"10.20517/jtgg.2024.02","DOIUrl":"https://doi.org/10.20517/jtgg.2024.02","url":null,"abstract":"Atypical neurofibromas (aNF) are peripheral nerve sheath tumors (PNSTs) histologically defined by cytologic atypia, hypercellularity, loss of neurofibroma architecture, and/or increased mitotic activity. aNF often have a heterozygous loss of CDKN2A/B in addition to homozygous NF1 loss. On MRI, aNF frequently appear as distinct nodular lesions, grow faster than plexiform neurofibromas, and have increased avidity on fluorodeoxyglucose positron emission tomography. At least some aNF are considered to be at greater risk for transformation to highly aggressive malignant PNSTs. We have observed that some PNSTs demonstrate a discrepancy between histological, clinical, and genomic criteria, where a PNST without histologically concerning findings may have clinical and imaging features concerning aNF and CDKN2A/B loss. This case series highlights this discrepancy and suggests the inclusion of CDKN2A/B loss to define aNF, along with clinical and imaging findings, to determine the potential for malignant transformation, and to select appropriate clinical management.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140673498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetics in the diagnosis and treatment of cardiovascular diseases 遗传学在心血管疾病诊断和治疗中的应用

Journal of translational genetics and genomics Pub Date : 2024-04-15 DOI: 10.20517/jtgg.2023.59

K. Bliden, Sahib Singh, Roni Shanoada, Isha Kalia, U. Tantry, Alyssa Zimmerman, A. D. Babu, Lekshminarayan Raghavakurup, Taylor Stude, Damian Sidorski, Paul A Gurbel

{"title":"Genetics in the diagnosis and treatment of cardiovascular diseases","authors":"K. Bliden, Sahib Singh, Roni Shanoada, Isha Kalia, U. Tantry, Alyssa Zimmerman, A. D. Babu, Lekshminarayan Raghavakurup, Taylor Stude, Damian Sidorski, Paul A Gurbel","doi":"10.20517/jtgg.2023.59","DOIUrl":"https://doi.org/10.20517/jtgg.2023.59","url":null,"abstract":"Cardiovascular diseases (CVDs) remain one of the leading causes of morbidity and mortality worldwide, with genetics being a major risk factor. Genetic cardiovascular disease can occur either because of single variant (Mendelian) or polygenic influences and has been linked to inherited cardiovascular conditions (ICC) such as arrhythmias, cardiomyopathies, dyslipidemias, and aortopathies which are significant factors leading to sudden cardiac death in young adults. Timely screening, diagnosis, and management of ICC can not only provide life-saving treatment to a patient, but also identify at-risk family members. The field of pharmacogenomics (PGx) helped to understand the variable action of medications such as clopidogrel, aspirin, warfarin, and statin according to genotype. Newer technologies such as multi-omics can combine data from multiple sources such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome. These advancements can contribute to the development of polygenic prediction scores and precision medicine tailored to individual genotypes. Substantial strides have been made in genetic-based therapeutics, gene editing technologies, and drug delivery systems, which have significantly expanded treatment options for patients with acquired or inherited CVDs. Although variable, the country- and society-specific guidelines on genetic testing for ICC and PGx and treatment are being continuously updated to keep up with ongoing research in the field. Along with appropriate knowledge, other factors including cost and availability of genetic testing play a vital role in the usage by both physicians and patients. With the advent of newer genetic testing for CVDs, a key factor is the availability of genetic counselors (GCs) who are specifically trained in cardiovascular genomics. The current review provides a concise summary of the major influences of genetics in the diagnosis and treatment of CVDs.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140700357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silent players, loud impact: unveiling the therapeutic potentials of LncRNAs 无声的参与者，巨大的影响：揭示 LncRNA 的治疗潜力

Journal of translational genetics and genomics Pub Date : 2024-04-07 DOI: 10.20517/jtgg.2023.55

Ahmed Kamal, M. Swellam, N. Shalaby, Marwa K. Darwish, E. El-Nahrery

引用次数: 0

Reduced protein kinase C delta in a high molecular weight complex in mitochondria and elevated creatine uptake into Barth syndrome B lymphoblasts. 线粒体中高分子复合体的蛋白激酶 C delta 减少，巴氏综合征 B 淋巴细胞的肌酸摄取量增加。

Journal of translational genetics and genomics Pub Date : 2024-01-01 Epub Date: 2024-05-29 DOI: 10.20517/jtgg.2024.11

Edgard M Mejia, Genevieve C Sparagna, Donald W Miller, Grant M Hatch

{"title":"Reduced protein kinase C delta in a high molecular weight complex in mitochondria and elevated creatine uptake into Barth syndrome B lymphoblasts.","authors":"Edgard M Mejia, Genevieve C Sparagna, Donald W Miller, Grant M Hatch","doi":"10.20517/jtgg.2024.11","DOIUrl":"10.20517/jtgg.2024.11","url":null,"abstract":"Aim: Barth syndrome (BTHS) is a rare X-linked genetic disease in which mitochondrial oxidative phosphorylation is impaired due to a mutation in the TAFAZZIN gene. The protein kinase C delta (PKCδ) signalosome exists as a high molecular weight complex in mitochondria and controls mitochondrial oxidative phosphorylation.Method: Here, we examined PKCδ levels in mitochondria of aged-matched control and BTHS patient B lymphoblasts and its association with a higher molecular weight complex in mitochondria.Result: Immunoblot analysis of blue-native polyacrylamide gel electrophoresis mitochondrial fractions revealed an increase in total PKCδ protein expression in BTHS lymphoblasts compared to controls. In contrast, PKCδ associated with a higher molecular weight complex was markedly reduced in BTHS patient B lymphoblasts compared to controls. Given the decrease in PKCδ associated with a higher molecular weight complex in mitochondria, we examined the uptake of creatine, a compound whose utilization is enhanced upon high energy demand. Creatine uptake was markedly elevated in BTHS lymphoblasts compared to controls.Conclusion: We hypothesize that reduced PKCδ within this higher molecular weight complex in mitochondria may contribute to the bioenergetic defects observed in BTHS lymphoblasts and that enhanced creatine uptake may serve as one of several compensatory mechanisms for the defective mitochondrial oxidative phosphorylation observed in these cells.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inborn errors of immunity present with neuropsychiatric symptoms overlapping with autistic behavioral symptoms 先天性免疫错误的神经精神症状与自闭症行为症状重叠

Journal of translational genetics and genomics Pub Date : 2023-12-22 DOI: 10.20517/jtgg.2023.32

Harumi Jyonouchi

{"title":"Inborn errors of immunity present with neuropsychiatric symptoms overlapping with autistic behavioral symptoms","authors":"Harumi Jyonouchi","doi":"10.20517/jtgg.2023.32","DOIUrl":"https://doi.org/10.20517/jtgg.2023.32","url":null,"abstract":"Autism spectrum disorder (ASD) is a behaviorally defined syndrome affected by multiple genetic and environmental factors. A wide variety of risk factors for ASD have been identified and many of these affect immune functions. This may not be surprising, since the immune system and the nervous system share common signaling mechanisms and affect each other as a part of the neuroimmune network. The ever-expanding scope of inborn errors of immunity (IEIs) has revealed multiple pathogenic gene variants that manifest overlapping clinical features of common neuropsychiatric diseases, including ASD. These IEIs often cause dysregulated immune activation and resultant chronic inflammation affecting multiple organs. Some IEIs also cause changes in morphogenesis and plasticity of the central nervous system. Such patients often present with a puzzling array of clinical features and some of them may be diagnosed with ASD or other neuropsychiatric conditions. The progress of our understanding of disease mechanisms for IEIs at the molecular levels has led to gene-specific treatment measures in some diseases. In addition, some ASD patients are found to have laboratory findings of neuroinflammation that resemble those seen in IEI patients. This may pave the way for applying specific treatment measures used for IEI patients in such ASD patients. This review focuses on describing IEIs that have overlapping features of ASD. Emphasis is also on IEIs that can be treated by targeting identified disease mechanisms. Such information may be helpful for clinicians who are considering genetic/metabolic workup in ASD patients.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138994119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Towards an understanding of the aetiology, genomic landscape and management of Moebius syndrome 了解莫比乌斯综合征的病因、基因组结构和治疗方法

Journal of translational genetics and genomics Pub Date : 2023-12-14 DOI: 10.20517/jtgg.2023.33

Ekaterina Lyulcheva-Bennett, Wendy Blumenow, Adelene O’Connor, Maria Kelly, Daimark Bennett, Adel Fattah

{"title":"Towards an understanding of the aetiology, genomic landscape and management of Moebius syndrome","authors":"Ekaterina Lyulcheva-Bennett, Wendy Blumenow, Adelene O’Connor, Maria Kelly, Daimark Bennett, Adel Fattah","doi":"10.20517/jtgg.2023.33","DOIUrl":"https://doi.org/10.20517/jtgg.2023.33","url":null,"abstract":"Moebius Syndrome (MBS) is a rare neurodevelopmental disorder characterised by facial paralysis and ocular motility defects. Its origins trace back to the 19th century, with its clinical delineation attributed to German neurologist Paul Möbius. The syndrome presents with a spectrum of variable systemic clinical features, necessitating a multidisciplinary approach to diagnosis and management. The prevalence of MBS has been estimated to range between 1 in 50,000 to 1 in 500,000 individuals, with a universal distribution across ethnicities and genders. The aetiology of MBS is poorly understood but is likely multifactorial, with developmental, genetic, and environmental factors playing roles. Recent research has identified potential genetic contributors, REV3L and PLXND1, but further work is needed to elucidate the genetic landscape of this rare neurodevelopmental disorder. Here we describe the current understanding of the clinical features, aetiology, genetic landscape, and management of MBS, emphasising the importance of early diagnosis and a holistic approach to patient care. We also propose a set of criteria aimed at standardising MBS reporting to enhance information sharing and bolster MBS research initiatives. Collaborative research efforts in the future hold the potential to offer transformative insights and improved outcomes for affected individuals and their families.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138971598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug-based approaches to modulate mitochondrial condition in the case of atherosclerosis: focus on correction of mitochondria dysfunction 在动脉粥样硬化病例中调节线粒体状况的药物方法：关注线粒体功能障碍的矫正

Journal of translational genetics and genomics Pub Date : 2023-12-07 DOI: 10.20517/jtgg.2023.38

Darina Gavrilova, Evgeny Bezsonov, Tatyana Degtyarevskaya

引用次数: 0

Targeting KIR as a novel approach to improve CAR-NK cell function 将 KIR 作为改善 CAR-NK 细胞功能的新方法

Journal of translational genetics and genomics Pub Date : 2023-12-05 DOI: 10.20517/jtgg.2023.25

Lara V. Graham, J. G. Fisher, S. Khakoo, Matthew D. Blunt

引用次数: 0

lncRNA involvement in immune-related diseases - from SNP association to implication in pathogenesis and therapeutic potential lncRNA 在免疫相关疾病中的参与--从 SNP 关联到发病机制和治疗潜力的影响

Journal of translational genetics and genomics Pub Date : 2023-11-27 DOI: 10.20517/jtgg.2023.14

Leire Bergara-Muguruza, A. Castellanos-Rubio, I. Santin, A. Olazagoitia-Garmendia

{"title":"lncRNA involvement in immune-related diseases - from SNP association to implication in pathogenesis and therapeutic potential","authors":"Leire Bergara-Muguruza, A. Castellanos-Rubio, I. Santin, A. Olazagoitia-Garmendia","doi":"10.20517/jtgg.2023.14","DOIUrl":"https://doi.org/10.20517/jtgg.2023.14","url":null,"abstract":"Development of new high throughput array-based techniques and, more recently, next-generation sequencing (NGS) technologies have revolutionized our capability to accurately characterize single nucleotide polymorphisms (SNPs) throughout the genome. These advances have facilitated large-scale genome-wide association studies (GWAS), which have served as fundamental elements in establishing links between SNPs and the susceptibility to several complex diseases, including those related to the immune system. Nevertheless, the molecular mechanisms underlying the development of most of these disorders are still poorly defined. Decoding the functionality of SNPs becomes increasingly challenging due to the predominant presence of these risk variants in non-coding regions of the genome. Among them, long non-coding RNAs (lncRNAs) are enriched in disease-associated SNPs. lncRNAs are involved in governing the control of gene expression both during transcription and at the post-transcriptional level. The existence of SNPs within the sequences of lncRNAs has the potential to alter their expression, structure, or function. This, in turn, can influence their regulatory roles and consequently contribute to the onset or progression of various diseases. In this review, we describe the implication of SNPs located in lncRNAs in the development of different immune-related diseases and highlight the potential of these molecules in the development of emerging RNA-based therapies.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139228416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0