Article
Genetics & Heredity
Yuheng Lang, Yue Zheng, Bingcai Qi, Weifeng Zheng, Chengxiu Zhao, Hu Zhai, Gang Wang, Zhiqiang Luo, Tong Li
Summary: This article presents a case of a female patient with Holt-Oram syndrome, who exhibited upper limb abnormalities and congenital heart defects. Genetic analysis revealed mutations in the TBX5 gene, and functional experiments demonstrated the role of TBX5 in cardiomyocytes.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Sandra D. Kikano, Wubishet Belay, Ann Kavanaugh-McHugh
Summary: This article describes a case of a fetus with isolated right atrial enlargement without tricuspid valve abnormalities and with small muscular VSDs, without other significant cardiac lesions. The persistent right atrial enlargement and relative fetal bradycardia without apparent AV block or other signs of abnormal conduction were observed on serial fetal echocardiograms. A postnatal diagnosis of Holt-Oram Syndrome was made. We suggest a comprehensive sonographic search for upper limb abnormalities and genetic evaluation in the setting of isolated right atrial enlargement.
PRENATAL DIAGNOSIS
(2023)
Article
Pediatrics
Guan-nan He, Xue-yan Wang, Min Kang, Xi-min Chen, Na Xi, Jing Zhao, Xi Chen
Summary: This case report describes a novel mutation in the TBX5 gene, previously unreported in China, expanding the known genetic variants associated with Holt-Oram syndrome (HOS).
FRONTIERS IN PEDIATRICS
(2021)
Editorial Material
Multidisciplinary Sciences
Xia Li, Weizhe Shi, Xuejiao Ding, Jingchun Li, Yiqiang Li, Tianying Nong, Hongwen Xu, Mingwei Zhu
Summary: This study reported a rare case of Holt-Oram syndrome with a common atrium and identified a novel small-insertion mutation in the TBX5 gene, suggesting its potential role as a disease-causing genetic variant in this family.
Article
Biochemistry & Molecular Biology
Debora Varela, Tatiana Varela, Natercia Conceicao, Angela Ferreira, Nuno Marques, Ana Paula Silva, Pedro Azevedo, Salome Pereira, Ana Camacho, Ilidio de Jesus, M. Leonor Cancela
Summary: Holt-Oram syndrome (HOS) is caused by pathogenic variants in the TBX5 gene, which includes heart and skeletal defects. Two novel TBX5 variants were identified in this study, with one causing severe cardiac phenotype and the other causing upper limb malformations. Functional analysis showed that both variants lead to a loss-of-function of TBX5.
MOLECULAR GENETICS AND GENOMICS
(2021)
Article
Genetics & Heredity
De-Gang Wang, Xing-Sheng Dong, Yi Xiong, Zhi-Ming Li, Ying-Jun Xie, Shu-Hua Liang, Tian-Hua Huang
Summary: A novel TBX5 gene variant potentially inducing Holt-Oram syndrome was identified. This variant affected normal splicing of TBX5 transcripts, upregulated TBX5 expression, and inhibited cellular activity.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Barbara Gonzalez-Teran, Maureen Pittman, Franco Felix, Reuben Thomas, Desmond Richmond-Buccola, Ruth Huttenhain, Krishna Choudhary, Elisabetta Moroni, Mauro W. Costa, Yu Huang, Arun Padmanabhan, Michael Alexanian, Clara Youngna Lee, Bonnie E. J. Maven, Kaitlen Samse-Knapp, Sarah U. Morton, Michael McGregor, Casey A. Gifford, J. G. Seidman, Christine E. Seidman, Bruce D. Gelb, Giorgio Colombo, Bruce R. Conklin, Brian L. Black, Benoit G. Bruneau, Nevan J. Krogan, Katherine S. Pollard, Deepak Srivastava
Summary: This study identifies genetic variants associated with congenital heart disease (CHD) and prioritizes and screens these variants using protein interactome analysis, leading to the identification of potential causative genes for CHD.
Article
Cell & Tissue Engineering
M. Dressen, H. Lahm, I. Neb, T. Luzius, S. A. Doppler, S. Schneider, E. Dzilic, R. Lange, M. Krane
Summary: The Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by upper limb malformation and congenital heart defects. In this study, adipose fibroblasts from a patient were reprogrammed using Sendai virus to generate fully pluripotent induced pluripotent stem cells (iPSCs).
STEM CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
A. M. U. B. Mahfuz, Md Arif Khan, Promita Deb, Sharmin Jahan Ansary, Rownak Jahan
Summary: TBX5 gene encodes the transcription factor TBX5, crucial for heart and limb development. This study identified 5 most damaging SNPs through in silico analyses, predicting their structural and functional consequences using various tools and predictors. Wet-lab experiments can further validate these findings regarding their potential role in causing Holt-Oram Syndrome.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2021)
Article
Genetics & Heredity
Camille Cenni, Stephanie Andres, Maja Hempel, Tim M. Strom, Ellen Thomas, Angela Davies, Norma Timoney, Alessandra Frigiola, Malcolm Logan, Muriel Holder-Espinasse
Summary: Holt-Oram syndrome (HOS) and Ulnar-Mammary syndrome (UMS) are rare autosomal dominant conditions caused by mutations in the TBX genes. This study reports a large German family with a duplication at 12q24.21 affecting both TBX5 and TBX3 genes, leading to a combination of HOS and UMS symptoms in affected individuals. This is the first report of a contiguous TBX3/TBX5 duplication associated with HOS/UMS phenotype.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Review
Endocrinology & Metabolism
Aneta Kodytkova, Petra Dusatkova, Shenali Anne Amaratunga, Lukas Plachy, Stepanka Pruhova, Jan Lebl
Summary: The thalidomide disaster in the late 1950s and early 1960s caused severe congenital malformations in over 10,000 children. It has been recently confirmed that the derivative of thalidomide, 5-hydroxythalidomide (5HT), in complex with the cereblon protein, interferes with early embryonic transcriptional regulation by selectively degrading SALL4. Pathogenic variants of the SALL4 gene can lead to genetic syndromes that mimic thalidomide embryopathy and result in various congenital malformations.
HORMONE RESEARCH IN PAEDIATRICS
(2023)
Article
Pediatrics
Kaori Yamoto, Fumiko Kato, Masaya Yamoto, Koji Fukumoto, Kenji Shimizu, Hirotomo Saitsu, Tsutomu Ogata
Summary: This study found that there is a correlation between pathogenic variants of the TBX5 gene and congenital tracheal stenosis.
CONGENITAL ANOMALIES
(2023)
Article
Orthopedics
Lori B. Ragni, Dan A. Zlotolow, Aaron Daluiski, Grace Kim
Summary: This case report presents the results of a long-term occupational therapy program for a patient with Holt-Oram syndrome (HOS) pre and postpollicization. The study shows improvement in passive and active range of motion as well as improved hand function after intervention. Comprehensive, long-term assessment is necessary to fully evaluate and communicate improvement.
JOURNAL OF HAND THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
Elizabeth Jordan, Laiken Peterson, Tomohiko Ai, Babken Asatryan, Lucas Bronicki, Emily Brown, Rudy Celeghin, Matthew Edwards, Judy Fan, Jodie Ingles, Cynthia A. James, Olga Jarinova, Renee Johnson, Daniel P. Judge, Najim Lahrouchi, Ronald H. Lekanne Deprez, R. Thomas Lumbers, Francesco Mazzarotto, Argelia Medeiros Domingo, Rebecca L. Miller, Ana Morales, Brittney Murray, Stacey Peters, Kalliopi Pilichou, Alexandros Protonotarios, Christopher Semsarian, Palak Shah, Petros Syrris, Courtney Thaxton, J. Peter van Tintelen, Roddy Walsh, Jessica Wang, James Ware, Ray E. Hershberger
Summary: A systematic curation of 51 genes related to DCM revealed that 19 genes have high evidence (12 definitive/strong, 7 moderate), but these genes only explain a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed.
Article
Cell & Tissue Engineering
H. Lahm, S. Stieglbauer, I. Neb, S. Doppler, S. Schneider, E. Dzilic, R. Lange, M. Krane, M. Dressen
Summary: TBX5 is a transcription factor that plays a crucial role in cardiogenesis. Mutations in this transcription factor can lead to conformational changes in the protein, causing non-specific or additional DNA binding. We introduced a patient-specific TBX5 mutation in a healthy induced pluripotent stem cell line and observed conformational changes in the protein, as well as ventricular septal defects. Additionally, we introduced a FLAG-tag on the mutated allele, creating a powerful tool to study altered TF activity binding.
STEM CELL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Axel Radlach Pries, Anastasia Naoum, Helmut Habazettl, Mathias Dunkel, Robert Preissner, Caroline J. Coats, Ana Tornada, Francesco Orso, Frans Van de Werf, David A. Wood, Frans Van de Werf, David A. Wood, Sophie O'Kelly, James Craven, Andrew Coats, Karin Sipido, Dirk De Backer, Lars Wallentin, Gerd Hasenfuss, Luigi della Sala, Ilaria Leggeri, David A. Wood, Frans Van de Werf, Tiny Jaarsma, Perry Elliott, Axel Radlach Pries, Rosalinda Madonna, Keld Kjeldsen, Aldo P. Maggioni, Oscar H. Franco, Sarah Hills, Francesca Pugliese, Dirk De Bacquer
EUROPEAN HEART JOURNAL
(2018)
Article
Cardiac & Cardiovascular Systems
Alice M. Jackson, Jonathan R. Dalzell, Niki L. Walker, Caroline J. Coats, Pardeep S. Jhund, Mark C. Petrie
Editorial Material
Cardiac & Cardiovascular Systems
Caroline J. Coats
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2018)
Article
Cardiac & Cardiovascular Systems
Caroline J. Coats, Menelaos Pavlou, Oliver T. Watkinson, Alexandros Protonotarios, Linda Moss, Rebecca Hyland, Khadija Rantell, Antonis A. Pantazis, Maite Tome, William J. McKenna, Michael P. Frenneaux, Rumana Omar, Perry M. Elliott
Article
Biochemical Research Methods
Gabriella Captur, Wendy E. Heywood, Caroline Coats, Stefania Rosmini, Vimal Patel, Luis R. Lopes, Richard Collis, Nina Patel, Petros Syrris, Paul Bassett, Ben O'Brien, James C. Moon, Perry M. Elliott, Kevin Mills
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Letter
Cardiac & Cardiovascular Systems
Caroline J. Coats, Michael P. Frenneaux, Perry M. Elliott
Article
Genetics & Heredity
Jenny Patterson, Diana Wellesley, Sian Morgan, Deirdre Cilliers, Stephanie Allen, Carol A. Gardiner
Summary: The diagnostic rate of prenatal CMA in the UK has shown improvement over time, with a pathogenic copy number variant identified in 7.8% of tests overall. Variants of uncertain significance (VUS) were reported in 0.7% of tests, and 'actionable' incidental findings in 0.12%. Reviewing survey responses at a national level highlights variations in testing experiences and practices, emphasizing the need for future guideline development and implementation of novel techniques such as prenatal whole exome sequencing.
PRENATAL DIAGNOSIS
(2021)
Article
Urology & Nephrology
Jenny Patterson, Zoe Jacob, Ben C. Reynolds
Summary: Monogenic causes of paediatric nephrocalcinosis can present with extensive phenotypic variability. In this case, a 14-year-old male with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies was confirmed to have Bartter syndrome type II through genetic investigation. The presence of amelogenesis imperfecta is rare in inherited tubulopathies, making this case exceptional in its presentation. The utility of a phenotype-driven genetic panel in resolving atypical presentations of nephrocalcinosis is highlighted, allowing for precise diagnosis, tailored therapy, and prognostication.
CLINICAL KIDNEY JOURNAL
(2022)
Editorial Material
Medicine, Research & Experimental
Julian D. Gillmore, Mary M. Reilly, Caroline J. Coats, Rob Cooper, Helen Cox, Mark R. E. Coyne, Andrew J. Green, Ruth McGowan, William E. Moody, Philip N. Hawkins
Summary: Diagnosing hereditary transthyretin-mediated amyloidosis (hATTR) is challenging due to the heterogeneity of clinical presentation. The TTR gene variant and its penetrance in each individual play a significant role in the clinical manifestations. There are specific TTR variants seen most commonly in the UK and Ireland, which require special consideration for diagnosis and genetic testing. A multidisciplinary panel of experts from the UK and Ireland developed a consensus statement, providing recommendations for diagnosis, screening, and management of hATTR, depending on the symptoms and genetic variants.
ADVANCES IN THERAPY
(2022)
Review
Cardiac & Cardiovascular Systems
Caroline J. Coats
Summary: The British Cardiovascular Society celebrates its centenary in 2022. It started as a small group of physicians interested in heart disease and has now grown into a professional organization representing cardiovascular care and research. The article outlines the history of the organization and discusses the impact of scientific and technological innovations on the medical world. It emphasizes the importance of addressing service needs, healthcare professionals, and healthcare policies, as well as improving healthcare standards.
Review
Cardiac & Cardiovascular Systems
John Bourke, Cathy Turner, William Bradlow, Ashish Chikermane, Caroline Coats, Matthew Fenton, Maria Ilina, Alexandra Johnson, Stam Kapetanakis, Lisa Kuhwald, Adrian Morley-Davies, Ros Quinlivan, Konstantinos Savvatis, Marianela Schiava, Zaheer Yousef, Michela Guglieri
Summary: This study provides concise evidence-based and/or consensus-based best practice guidance for cardiac care in children with DMD and recommendations for screening and management of female carriers of DMD gene mutations. These guidelines aim to improve heart health in DMD patients and promote uniform and high-level care through timely interventions.
Article
Cardiac & Cardiovascular Systems
Martin S. Maron, Ahmad Masri, Lubna Choudhury, Iacopo Olivotto, Sara Saberi, Andrew Wang, Pablo Garcia-Pavia, Neal K. Lakdawala, Sherif F. Nagueh, Florian Rader, Albree Tower-Rader, Aslan T. Turer, Caroline Coats, Michael A. Fifer, Anjali Owens, Scott D. Solomon, Hugh Watkins, Roberto Barriales-Villa, Christopher M. Kramer, Timothy C. Wong, Sharon L. Paige, Stephen B. Heitner, Stuart Kupfer, Fady I. Malik, Lisa Meng, Amy Wohltman, Theodore Abraham
Summary: This study evaluated the safety and efficacy of aficamten in patients with obstructive hypertrophic cardiomyopathy (oHCM). The results showed that aficamten significantly reduced left ventricular outflow tract gradients and improved clinical symptoms.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Caroline J. Coats, Wendy E. Heywood, Alex Virasami, Nadia Ashrafi, Petros Syrris, Cris dos Remedios, Thomas A. Treibel, James C. Moon, Luis R. Lopes, Christopher G. A. McGregor, Michael Ashworth, Neil J. Sebire, William J. McKenna, Kevin Mills, Perry M. Elliott
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2018)