Article
Genetics & Heredity
Yuchen Chang, Julie Wacker, Jodie Ingles, Ivan Macciocca, Ingrid King, Christopher Semsarian, Julie Mcgaughran, Robert G. Weintraub, Richard D. Bagnall
Summary: TBX20 is a cardiac transcription factor associated with atrial septal defects. Loss-of-function variants in TBX20 have been found in families with left ventricular non-compaction cardiomyopathy (LVNC). We report four families with TBX20 loss-of-function variants that segregate with LVNC. Our data strengthen the association between TBX20 loss-of-function variants and LVNC, and support the inclusion of TBX20 in genetic testing for LVNC.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Medicine, Research & Experimental
Kara D. Brodie, Elizabeth N. Liao, Michelle M. Florentine, Dylan K. Chan
Summary: This study evaluates the association between genetic diagnoses and hearing loss intervention. The results show that children diagnosed with a genetic diagnosis are significantly more likely to subsequently utilize hearing aids or cochlear implantation. This provides additional support for the importance of genetic testing in the evaluation and treatment of sensorineural hearing loss.
Review
Genetics & Heredity
Daria Grafodatskaya, Darren D. O'Rielly, Karine Bedard, Darci T. Butcher, Christopher J. Howlett, Alice Lytwyn, Elizabeth McCready, Jillian Parboosingh, Elizabeth L. Spriggs, Andrea K. Vaags, Tracy L. Stockley
Summary: This document provides considerations and recommendations for Canadian clinical laboratories developing, validating, and offering next-generation sequencing (NGS)-based BRCA1/2 tumor testing in ovarian cancers. It was drafted by the Canadian College of Medical Geneticists (CCMG) BRCA Ad Hoc Working Group and representatives from the Canadian Association of Pathologists, and approved by the CCMG board of directors. However, the current CCMG Practice Guidelines do not include all the information laboratories should consider when validating and using NGS for BRCA1/2 tumor testing in ovarian cancers.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Medicine, Research & Experimental
Hager Jaouadi, Chris Jopling, Fanny Bajolle, Alexis Theron, Adele Faucherre, Hilla Gerard, Sarab Al Dybiat, Caroline Ovaert, Damien Bonnet, Jean-Francois Avierinos, Stephane Zaffran
Summary: This study analyzed genetic variants in a cohort of BAV patients and found that only 10% of adult BAV patients had missense variants in ROBO and SLIT genes, while 61% of pediatric cases carried variants in these genes. Family segregation analysis showed that the ROBO4 gene variants followed an autosomal recessive pattern of inheritance. These findings suggest that the ROBO4 gene is not only implicated in BAV, but also in ToF.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Brandon Chalazan, Emma Freeth, Arezoo Mohajeri, Krishnan Ramanathan, Matthew Bennett, Jagdeep Walia, Laura Halperin, Thomas Roston, Julieta Lazarte, Robert A. Hegele, Anna Lehman, Zachary Laksman
Summary: This study aims to determine the prevalence of likely pathogenic and pathogenic variants from AF genes in early-onset AF patients. The results suggest a potential clinical utility for offering different screening and treatment regimens in AF patients with a genetic defect.
EUROPEAN JOURNAL OF HUMAN GENETICS
(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)
Article
Cardiac & Cardiovascular Systems
A. J. Marian
Summary: Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by left ventricular hypertrophy and may lead to heart failure or sudden cardiac death. Pathogenic variants in genes encoding myocardial protein constituents, especially MYH7 and MYBPC3 genes, are the main causes of HCM. Advances in genetic testing and drug development have improved the therapeutic prospects for HCM.
CIRCULATION RESEARCH
(2021)
Article
Medicine, General & Internal
Yuan Jin, Xiaozhou Liu, Sen Chen, Jiale Xiang, Zhiyu Peng, Yu Sun
Summary: The study aimed to improve the etiological diagnosis of congenital hearing loss by combining whole-exome sequencing with cytomegalovirus testing. It found that some children had genetic variants that may cause deafness, and some patients also carried deafness gene variants associated with a syndrome.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Genetics & Heredity
Lisa Pavinato, Marina Villamor-Paya, Maria Sanchiz-Calvo, Cristina Andreoli, Marina Gay, Marta Vilaseca, Gianluca Arauz-Garofalo, Andrea Ciolfi, Alessandro Bruselles, Tommaso Pippucci, Valentina Prota, Diana Carli, Elisa Giorgio, Francesca Clementina Radio, Vincenzo Antona, Mario Giuffre, Kara Ranguin, Cindy Colson, Silvia De Rubeis, Paola Dimartino, Joseph D. Buxbaum, Giovanni Battista Ferrero, Marco Tartaglia, Simone Martinelli, Travis H. Stracker, Alfredo Brusco
Summary: This study identified novel TLK2 pathogenic variants associated with MRD57, expanding our knowledge of TLK2 function and its role in neurodevelopmental disorders.
JOURNAL OF MEDICAL GENETICS
(2022)
Review
Cell Biology
You-Wei Wang, Nan Hu, Xiao-Hong Li
Summary: Revealing the mechanisms of neural development and neural diseases is a challenging task in life science. Brain organoids derived from pluripotent stem cells can mimic the development, function, and signal generation of human brains, providing a unique advantage for studying neurology. Single-cell RNA sequencing and multielectrode array analysis have shown the similarity between brain organoids and the immature human brain at early developmental stages.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
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
Weilai Dong, Hande Kaymakcalan, Sheng Chih Jin, Nicholas S. Diab, Cansaran Tanidir, Ali Seyfi Yalim Yalcin, A. Gulhan Ercan-Sencicek, Shrikant Mane, Murat Gunel, Richard P. Lifton, Kaya Bilguvar, Martina Brueckner
Summary: The genome analysis study of CHD in consanguineous families in Turkey reveals a unique genetic architecture, where consanguinity has a strong contribution to laterality defects. This study provides valuable information about the genetic landscape of CHD in consanguineous families in Turkey.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Tong Yi, Xiaoyan Hao, Hairui Sun, Ye Zhang, Jiancheng Han, Xiaoyan Gu, Lin Sun, Xiaowei Liu, Ying Zhao, Yong Guo, Xiaoxue Zhou, Yihua He
Summary: CNV-seq and ES can provide valuable information for genetic evaluation of foetal CHDs. Nearly 1/3 of the foetal CHD cases were found to have genetic abnormalities. AVSD, LVOTO, and CTD were the most common CHD categories, and mutations in KMT2D, CHD7, and NOTCH1 were frequently observed.
Article
Cell Biology
Polakit Teekakirikul, Wenjuan Zhu, Xinxiu Xu, Cullen B. Young, Tuantuan Tan, Amanda M. Smith, Chengdong Wang, Kevin A. Peterson, George C. Gabriel, Sebastian Ho, Yi Sheng, Anne Moreau de Bellaing, Daniel A. Sonnenberg, Jiuann-huey Lin, Elisavet Fotiou, Gennadiy Tenin, Michael X. Wang, Yijen L. Wu, Timothy Feinstein, William Devine, Honglan Gou, Abha S. Bais, Benjamin J. Glennon, Maliha Zahid, Timothy C. Wong, Ferhaan Ahmad, Michael J. Rynkiewicz, William J. Lehman, Bernard Keavney, Tero-Pekka Alastalo, Mary-Louise Freckmann, Kyle Orwig, Steve Murray, Stephanie M. Ware, Hui Zhao, Brian Feingold, Cecilia W. Lo
Summary: Analysis of large-scale human genomic data has identified a rare lethal mutation TPM1 that causes large atrial septal defect (ASD). The study also reveals a candidate suppressor variant TLN2 that can mitigate the disease symptoms caused by TPM1 mutation.
CELL REPORTS MEDICINE
(2022)
Article
Cell Biology
Qianqian Liang, Siqing Wang, Xinyan Zhou, Yongbo Li, Shenghui Xing, Yi'ou Sha, Fuling Yang, Wenjun Huang, Nanbo Liu, Zhetao Li, Yufei Chen, Yichi Xu, Ping Zhu, Fei Lan, Ning Sun
Summary: Heart development is controlled by a complex transcriptional network involving transcription factors and epigenetic regulators. A study found that MESP1 interacts with RING1A/RING1, the core component of PRC1, and activates cardiogenic genes through cohesin and CTCF-mediated promoter-enhancer interactions and p300-mediated histone acetylation. Mutations in MESP1, PRC1, and cohesin components can lead to cardiac abnormalities.
DEVELOPMENTAL CELL
(2022)