Article
Medicine, General & Internal
Hong-Yu Shi, Meng-Shi Xie, Chen-Xi Yang, Ri-Tai Huang, Song Xue, Xing-Yuan Liu, Ying-Jia Xu, Yi-Qing Yang
Summary: Congenital heart disease (CHD) is the most common birth deformity and a leading cause of neonatal mortality worldwide. Although some genes have been found to be involved in the pathogenesis of CHD, the genetic components predisposing to CHD in most cases remain unclear. This study identified a new variation in the SOX18 gene associated with CHD and found that it lost transactivation and synergistic activation with other genes responsible for CHD.
Review
Cell Biology
Kavitha S. Rao, Vasumathi Kameswaran, Benoit G. Bruneau
Summary: Congenital heart defects are common birth defects with unknown causes. Recent development of experimental models, including mouse models and human cellular models, have helped to enhance our understanding of the molecular basis of these defects. The development of cardiac organoids also shows promise in creating more anatomically informative human models of congenital heart defects.
GENES & DEVELOPMENT
(2022)
Article
Genetics & Heredity
Wei-Zhen Zhou, Wenke Li, Huayan Shen, Ruby W. Wang, Wen Chen, Yujing Zhang, Qingyi Zeng, Hao Wang, Meng Yuan, Ziyi Zeng, Jinhui Cui, Chuan-Yun Li, Fred Y. Ye, Zhou Zhou
Summary: This study developed an evidence-based knowledgebase of congenital heart disease (CHD) that provides comprehensive information on CHD-related genes and clinical manifestations. Through the integration of data from 1114 publications, it links 1124 susceptibility genes and 3591 variations to over 300 CHD types and related syndromes. The knowledgebase also includes functional annotations from 50 databases/tools to facilitate the interpretation of gene and variation effects on disease pathogenicity. A core CHD sub-network of 163 genes was extracted using a gene interaction network approach. Overall, CHDbase is a valuable resource for studying CHD susceptibilities.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Genetics & Heredity
Hong-Yu Shi, Meng-Shi Xie, Yu-Han Guo, Chen-Xi Yang, Jia-Ning Gu, Qi Qiao, Ruo-Min Di, Xing-Biao Qiu, Ying-Jia Xu, Yi-Qing Yang
Summary: Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, is characterized by ventricular dilation and systolic dysfunction. This study identified a novel heterozygous mutation in the VEZF1 gene in a family with DCM. Functional analysis revealed that the mutant VEZF1 protein failed to activate the promoters of MYH7 and ET1 genes, which are associated with DCM. These findings provide new insight into the molecular pathogenesis of DCM and have potential implications for personalized medical management of DCM patients.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Lan Zhao, Wei-Feng Jiang, Chen-Xi Yang, Qi Qiao, Ying-Jia Xu, Hong-Yu Shi, Xing-Biao Qiu, Shao-Hui Wu, Yi-Qing Yang
Summary: This study identified a new SOX17 gene variation associated with familial CHD, providing novel insights into the molecular mechanism of CHD, and suggesting potential implications for individualized prevention and genetic risk assessment of affected family members.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Robert S. Leigh, Mika J. Valimaki, Bogac L. Kaynak, Heikki J. Ruskoaho
Summary: Heart formation requires transcriptional regulators and fetal gene program. Missense variants of congenital heart disease (CHD) disrupt specific protein domains, leading to CHDs. Chemical screening, gene expression analysis, and in vitro study identified a TAF1 bromodomain inhibitor, which modulates cardiac transcription and reveals an epigenetically-driven CHD mechanism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Health Care Sciences & Services
Olga Maria Diz, Rocio Toro, Sergi Cesar, Olga Gomez, Georgia Sarquella-Brugada, Oscar Campuzano
Summary: Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels, with genetic variants playing a key role. High-throughput genetic technologies can help identify pathogenic factors. Early diagnosis and personalized treatment are crucial due to the high incidence and associated complications.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Physiology
Nouf J. Althali, Kathryn E. Hentges
Summary: Congenital heart defects refer to structural abnormalities of the heart or blood vessels present at birth, affecting approximately 1% of newborns worldwide. Tetralogy of Fallot is the most common cyanotic congenital heart abnormality, accounting for 5-10% of all congenital cardiac defects. While some cases of TOF are associated with known diseases or chromosomal abnormalities, the majority are non-syndromic and have unknown causes.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Lea Linglart, Damien Bonnet
Summary: Congenital heart disease is a common condition, but its pathophysiology is still unclear. Only about 35% of cases can be explained by a definitive genetic origin. The embryonic development of the heart involves a multi-level regulatory network that is susceptible to outside disruption, leading to developmental defects. Additionally, the heart's development is closely related to mechanical stimulation, and disruptions in the intrauterine environment can directly affect fetal development.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2022)
Review
Cardiac & Cardiovascular Systems
Minh B. Nguyen, Seema Mital, Luc Mertens, Aamir Jeewa, Mark K. Friedberg, Julien Aguet, Arnon Adler, Christopher Z. Lam, Andreea Dragulescu, Harry Rakowski, Olivier Villemain
Summary: This review examines the association between genetic variations and outcomes in pediatric hypertrophic cardiomyopathy (HCM), discussing current approaches to phenotyping cardiovascular characteristics and exploring potential avenues for improving risk assessment of sudden cardiac death in children with HCM.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Biochemistry & Molecular Biology
Justin Koesterich, Joon-Yong An, Fumitaka Inoue, Ajuni Sohota, Nadav Ahituv, Stephan J. Sanders, Anat Kreimer
Summary: Autism spectrum disorder (ASD) is influenced by both common and rare genetic variations, with disruptive rare variants in protein-coding regions having a clear impact on symptoms. However, the role of rare non-coding variants, including promoters, remains unclear. In this study, the functional impact of de novo mutations in promoter regions in ASD cases and controls was analyzed using massively parallel reporter assays. Although certain functionally high confidence de novo variants were identified, no differences in functional impact based on ASD diagnostic status were found.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Xiaoliang Li, Guocheng Shi, Yang Li, Xiaoqing Zhang, Ying Xiang, Teng Wang, Yanxin Li, Huiwen Chen, Qihua Fu, Hong Zhang, Bo Wang
Summary: CNV is an important pathogenic factor of congenital heart disease (CHD). This study identified a significant association between 15q11.2 deletion and TAPVC, characterized the gene expression profile that might arise from the deletion for a TAPVC family using cell experiments.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
Xiang Zhang, Giang Thi Hien Nham, Kazuo Ito, Tamayuki Shinomura
Summary: This study aimed to clarify the transcriptional complex formed at each enhancer region in the COL2A1 gene by identifying specific transcription factors that bind to each enhancer element. The discovery of KLF4 and ARID5B as new binding proteins, as well as the need for further studies on factors binding to the E2 enhancer element, provide important insights into the molecular mechanisms underlying COL2A1 regulation.
Review
Cardiac & Cardiovascular Systems
Patryk Leczycki, Maciej Banach, Marek Maciejewski, Agata Bielecka-Dabrowa
Summary: In recent decades, there has been a significant increase in the number of adults with congenital heart diseases (ACHD), necessitating thorough evaluation of their current condition. There is currently a lack of universal parameters or scales to easily assess the deterioration of ACHD patients' condition, emphasizing the need to identify widely available, cost-effective, and user-friendly factors. Studies have shown potential prognostic factors including echocardiography and magnetic resonance imaging, cardiopulmonary exercise testing, and biomarkers. However, further research is needed to create a specific assessment panel for patients with specific congenital heart diseases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Genetics & Heredity
Yin Wang, Ying-Jia Xu, Chen-Xi Yang, Ri-Tai Huang, Song Xue, Fang Yuan, Yi-Qing Yang
Summary: Congenital heart disease (CHD) is the most common developmental deformity in humans, causing significant morbidity and mortality worldwide. A study investigated a four-generation CHD family and identified a heterozygous variation in the SMAD4 gene, which is associated with autosomal-dominant CHD. Functional experiments revealed the potential involvement of SMAD4 in CHD pathogenesis. These findings have potential implications for the prevention and prognosis of CHD.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)