Medizinische Genetik最新文献

Cardiac arrhythmias and genetics - current stage. 心律失常和遗传学-当前阶段。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2006

Schulze-Bahr, Sven Dittmann, Janis Kerkering

{"title":"Cardiac arrhythmias and genetics - current stage.","authors":"Schulze-Bahr, Sven Dittmann, Janis Kerkering","doi":"10.1515/medgen-2025-2006","DOIUrl":"10.1515/medgen-2025-2006","url":null,"abstract":"Recently, cardiogenetics is a rapidly developing medical section combining cardiovascular and genetic knowledge. Inherited forms of cardiac arrhythmias are typically rare diseases (prevalence < 1:2,000) and may occur in a sporadic or familial manner, here mostly in an autosomal dominant form. They are also called \"primary electrical heart disorders\" due to the ECG-based diagnosis and mainly normal cardiac imaging, i.e. absence of structural heart abnormalities. Their genetic basis is heterogeneous, still incomplete (variant detection rates between 10 % and 80 %) and mostly related to cardiac ion channel genes and related regulatory units. So far, the utility of polygenic risk scores is under current evaluation. Clinical disease expressivity may range from non-penetrance to high penetrance, indicating the importance of additional clinical modifiers (genetic and non-genetic) that modulate phenotypic signs. Occurrence of symptoms, as typical for other ion channel disorders (e.g., epilepsy), also depends on exposure to specific and often genotype-related environmental triggers, that enhance the occurrence of clinically relevant and potentially life-threatening arrhythmias. In the following, the main focus is on cardiac ion channel disorders, with regard to some general genetic aspects and current guidelines indicating the value of genotyping to support early disease recognition, confirmation of diagnosis and prevention of severe cardiac events.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 2","pages":"125-136"},"PeriodicalIF":1.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disease mechanism and novel drug therapies for atrial fibrillation. 房颤的发病机制及新型药物治疗。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2005

Constanze Schmidt, Felix Wiedmann

引用次数: 0

Cardiovascular aspects of Noonan syndrome and related disorders. 努南综合征及相关疾病的心血管方面。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2010

Martin Zenker, Cordula M Wolf

{"title":"Cardiovascular aspects of Noonan syndrome and related disorders.","authors":"Martin Zenker, Cordula M Wolf","doi":"10.1515/medgen-2025-2010","DOIUrl":"10.1515/medgen-2025-2010","url":null,"abstract":"Noonan syndrome and other RASopathies constitute an important group of disorders to be considered in the differential diagnosis in individuals with congenital heart defects and hypertrophic cardiomyopathy. The cardiovascular phenotype of RASopathies is complex and comprises a spectrum of abnormalities, including not only congenital defects but also abnormalities affecting the lymphovascular system and other anomalies of the vascular system, which may emerge over the course of an individual's lifetime. Affected individuals typically present with a syndromic phenotype, exhibiting additional physical symptoms outside of the cardiovascular system and neuropsychological deficits. Genetic testing of the established disease genes for RASopathies is an effective method for identifying the underlying genetic variant in the majority of cases. This approach is strongly recommended to facilitate a more precise prognosis and the potential for personalized targeted therapies. Screening for RASopathy-associated gene variants in individuals with isolated CHDs, HCM, or other isolated cardiovascular features outside the NS spectrum appears to have limited clinical utility. However, it should be noted that the RASopathy phenotype may be challenging to discern in cases of mild or oligosymptomatic involvement, or it may be obscured by the presence of severe medical conditions, particularly in very young children.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 2","pages":"113-124"},"PeriodicalIF":1.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding inherited cardiomyopathies: clinical aspects and genetic determinants. 了解遗传性心肌病：临床方面和遗传决定因素。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2007

Gökhan Yigit, Silke Kaulfuß, Bernd Wollnik

{"title":"Understanding inherited cardiomyopathies: clinical aspects and genetic determinants.","authors":"Gökhan Yigit, Silke Kaulfuß, Bernd Wollnik","doi":"10.1515/medgen-2025-2007","DOIUrl":"10.1515/medgen-2025-2007","url":null,"abstract":"Cardiomyopathies (CMs) are a clinically heterogeneous group of cardiovascular diseases characterized by structural and functional abnormalities of the heart muscle in the absence of coronary artery disease, hypertension, valve disease, or congenital heart disease as a leading cause. The phenotypic spectrum of CMs ranges from silent heart failure to symptomatic heart failure and sudden cardiac death, and CMs are one of the leading causes of cardiovascular morbidity worldwide. CMs are highly heritable, although a clear distinction between inherited and acquired forms remains challenging, particularly due to observed incomplete penetrance and variable expressivity of inherited CMs. Based on their specific morphological phenotypes and functional characteristics, CMs can be divided into at least 5 different subgroups: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic cardiomyopathy (ACM), restrictive cardiomyopathy (RCM), and (left ventricular) non-compaction cardiomyopathy (LVNC), which show both clinical as well as genetic overlap. Since the identification of pathogenic variants in MYH7 as a genetic cause of HCM in 1990, enormous progress has been made in understanding genetic factors contributing to cardiomyopathies. Currently, over 100 genes have been associated with at least one of the CM subtypes, providing a deeper understanding of the cellular basis of genetic heart failure syndromes, unveiling new insights into the molecular biology of heart function in both health and disease, and, thereby, facilitating the development of novel therapeutic strategies and personalized treatment approaches.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 2","pages":"103-111"},"PeriodicalIF":1.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current and future diagnostics of congenital heart disease (CHD). 先天性心脏病（CHD）的当前和未来诊断。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2008

Marc-Phillip Hitz, Gregor Dombrowsky, Nico Melnik, Chiara Vey

{"title":"Current and future diagnostics of congenital heart disease (CHD).","authors":"Marc-Phillip Hitz, Gregor Dombrowsky, Nico Melnik, Chiara Vey","doi":"10.1515/medgen-2025-2008","DOIUrl":"10.1515/medgen-2025-2008","url":null,"abstract":"Congenital heart defects (CHD) are one of the most common anomalies found among live births and represent a complex multifactorial condition. Given that more than 90 % of cases survive due to improved early treatment options (e.g., catheter intervention, surgical procedure, and improved intensive care), genotype-informed patient follow-up should consider lifelong treatment considering different types of comorbidities. Unfortunately, a thorough genetic workup is only offered to a minority of CHD patients. However, a comprehensive understanding of the genetic underpinnings combined with in-depth phenotyping would strengthen our knowledge regarding the impact of environmental (e.g., pre-gestational diabetes) and genetic causes ranging from aneuploidies to single variants and more complex inheritance patterns on early heart development. Therefore, comprehensive genetic analysis in these patients is an essential way of predicting the prognosis and recurrence risk in families and ultimately improving patients' quality of life due to better therapeutic options. In this review, we examine the different types of variants and genes of different molecular genetics techniques to assess the diagnostic yield in different CHD sub-phenotypes. Given the complex inheritance pattern observed in CHD, we also consider possible future methods and frameworks to improve diagnostics and allow for better genotype-phenotype correlation in this patient group. Predicting recurrence risk and prognosis in CHD patients will ultimately allow for better treatment and lifelong therapeutic outcomes for CHD patients.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 2","pages":"95-102"},"PeriodicalIF":1.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to: Long-term experience with gene augmentation therapy in patients with inherited retinal disease associated with biallelic mutations in RPE65. 对与RPE65双等位基因突变相关的遗传性视网膜疾病患者进行基因增强治疗的长期经验的更正。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2012

Birgit Lorenz

引用次数: 0

S1-Leitlinie zum "pränatalen Schnelltest". “S1：产前快速检测”。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2011

引用次数: 0

Advances in human induced pluripotent stem cell (hiPSC)-based disease modelling in cardiogenetics. 基于人类诱导多能干细胞（hiPSC）的心脏遗传学疾病建模研究进展。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI: 10.1515/medgen-2025-2009

Sandra Hoffmann, Timon Seeger

{"title":"Advances in human induced pluripotent stem cell (hiPSC)-based disease modelling in cardiogenetics.","authors":"Sandra Hoffmann, Timon Seeger","doi":"10.1515/medgen-2025-2009","DOIUrl":"10.1515/medgen-2025-2009","url":null,"abstract":"Human induced pluripotent stem cell (hiPSC)-based disease modelling has significantly advanced the field of cardiogenetics, providing a precise, patient-specific platform for studying genetic causes of heart diseases. Coupled with genome editing technologies such as CRISPR/Cas, hiPSC-based models not only allow the creation of isogenic lines to study mutation-specific cardiac phenotypes, but also enable the targeted modulation of gene expression to explore the effects of genetic and epigenetic deficits at the cellular and molecular level. hiPSC-based models of heart disease range from two-dimensional cultures of hiPSC-derived cardiovascular cell types, such as various cardiomyocyte subtypes, endothelial cells, pericytes, vascular smooth muscle cells, cardiac fibroblasts, immune cells, etc., to cardiac tissue cultures including organoids, microtissues, engineered heart tissues, and microphysiological systems. These models are further enhanced by multi-omics approaches, integrating genomic, transcriptomic, epigenomic, proteomic, and metabolomic data to provide a comprehensive view of disease mechanisms. In particular, advances in cardiovascular tissue engineering enable the development of more physiologically relevant systems that recapitulate native heart architecture and function, allowing for more accurate modelling of cardiac disease, drug screening, and toxicity testing, with the overall goal of personalised medical approaches, where therapies can be tailored to individual genetic profiles. Despite significant progress, challenges remain in the maturation of hiPSC-derived cardiomyocytes and the complexity of reproducing adult heart conditions. Here, we provide a concise update on the most advanced methods of hiPSC-based disease modelling in cardiogenetics, with a focus on genome editing and cardiac tissue engineering.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 2","pages":"137-146"},"PeriodicalIF":1.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic testing in the genetically complex age-related macular degeneration. 遗传复杂的老年性黄斑变性的诊断试验。

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-02-12 eCollection Date: 2025-04-01 DOI: 10.1515/medgen-2024-2064

Christina Kiel, Bernhard H F Weber

引用次数: 0

Long-term experience with gene augmentation therapy in patients with inherited retinal disease associated with biallelic mutations in RPE65. 基因增强治疗与RPE65双等位基因突变相关的遗传性视网膜疾病患者的长期经验

IF 1.1 4区生物学

Medizinische Genetik Pub Date : 2025-02-12 eCollection Date: 2025-04-01 DOI: 10.1515/medgen-2024-2067

Birgit Lorenz

{"title":"Long-term experience with gene augmentation therapy in patients with inherited retinal disease associated with biallelic mutations in RPE65.","authors":"Birgit Lorenz","doi":"10.1515/medgen-2024-2067","DOIUrl":"10.1515/medgen-2024-2067","url":null,"abstract":"RPE65 biallelic mutation-associated inherited retinal degeneration (IRD) is currently the only IRD for which gene therapy is approved. This narrative review provides a brief overview of the disease and an update of the current literature on outcomes following the approval of treatment with voretigene neparvovec (LuxturnaTM) in 2017 (USA) and Europe (2018). Post-marketing results confirm a significant therapeutic effect of this gene augmentation on rod function similar to that seen in the phase 1 to 3 clinical trials. The full-field chromatic light sensitivity test is an appropriate test to demonstrate early and sustained effects of treatment. Visual acuity and visual fields may improve in less advanced disease. Accelerated chorioretinal atrophy (CRA) is a previously unrecognised adverse effect that is now reported in 13 % to 50 % of treated eyes. If central, visual acuity loss and paracentral visual field defects may occur. Further studies are needed to identify patients at risk of CRA in order to maximize patient benefit from a costly intervention.","PeriodicalId":51130,"journal":{"name":"Medizinische Genetik","volume":"37 1","pages":"47-56"},"PeriodicalIF":1.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0