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
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
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
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
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
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
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
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
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 Biology
Irfan S. Kathiriya, Kavitha S. Rao, Giovanni Iacono, W. Patrick Devine, Andrew P. Blair, Swetansu K. Hota, Michael H. Lai, Bayardo Garay, Reuben Thomas, Henry Z. Gong, Lauren K. Wasson, Piyush Goyal, Tatyana Sukonnik, Kevin M. Hu, Gunes A. Akgun, Laure D. Bernard, Brynn N. Akerberg, Fei Gu, Kai Li, Matthew L. Speir, Maximilian Haeussler, William T. Pu, Joshua M. Stuart, Christine E. Seidman, J. G. Seidman, Holger Heyn, Benoit G. Bruneau
Summary: Lower dosage of the CHD transcription factor TBX5 results in highly sensitive dysregulation in discrete subsets of iPSC-derived cardiomyocytes, affecting pathways related to heart development, cardiomyocyte function, and CHD genetics, and potentially leading to the occurrence of congenital heart diseases.
DEVELOPMENTAL CELL
(2021)
Article
Cell Biology
Michael G. Mfarej, Caitlin A. Hyland, Annie C. Sanchez, Matthias M. Falk, M. Kathryn Lovine, Robert V. Skibbens
Summary: Cohesins are ATPase complexes that play crucial roles in various cellular processes. Cohesinopathies result from mutations in cohesin proteins or regulators, leading to a range of developmental disorders. Understanding the signaling networks associated with cohesin-dependent pathways is important for treating cohesinopathies, especially in relation to cardiac defects. This article highlights the alterations in cohesins and cohesin regulators, emphasizing their impact on heart defects and proposing a new perspective on the underlying mechanisms.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Surgery
Ana Gabriela Auquilla, Fernanda Patricia Llanos, Luis Enrique Marcano Sanz, Miurkis Endis, Maria Isabel Ruilova, Sofia Molina, Cesar Patino
Summary: The article describes a rare malformation of the aortic arch, in which the left carotid artery anomalously originates from the pulmonary artery, with the patient also having Holt Oram syndrome. Surgical treatment options include reimplantation of the artery or ligation of the abnormal vessel, with the patient showing favorable evolution and remaining asymptomatic after two years of follow-up.
CIRUGIA CARDIOVASCULAR
(2021)
Article
Pediatrics
Abhilasha Singh Panwar, Amar Taksande, Syed Athhar Saqqaf, Revat Meshram
Summary: Holt-Oram syndrome is an autosomal dominant disorder caused by a mutation in the TBX5 gene, leading to malformations in the upper limb and heart such as atrial septal defect. We present a rare case of HOS in a three-year-old child with atrial septal defect, ventricular septal defect, and severe pulmonary arterial hypertension.
INTERNATIONAL JOURNAL OF PEDIATRICS-MASHHAD
(2021)