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
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
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)
Review
Plant Sciences
Praveen Kumar Kathare, Enamul Huq
Summary: The article summarizes the role of phytochromes in regulating plant growth and development, particularly in the regulation of pre-mRNA splicing process.
CURRENT OPINION IN PLANT BIOLOGY
(2021)
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.
Review
Biochemistry & Molecular Biology
Sierra L. L. Love, Joseph D. D. Emerson, Kazunori Koide, Aaron A. A. Hoskins
Summary: Pre-mRNA splicing is a crucial step in human gene expression, carried out by a macromolecular machine known as the spliceosome. Mutations in this machinery can lead to various human diseases. This review provides an overview of the main features of the pre-mRNA splicing machinery in humans and how changes in its components' function can result in diseases ranging from blindness to cancers. The article also discusses drugs that interact with the spliceosome to alter splicing outcomes and speculates on future treatments for spliceosomopathies.
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
Isabella E. Maudlin, Jean D. Beggs
Summary: The study revealed that in yeast, Bur1 kinase enhances co-transcriptional spliceosome assembly and pre-mRNA splicing by augmenting Spt5 phosphorylation, while depletion of Ctk1 kinase does not affect these processes.
Article
Biochemistry & Molecular Biology
Laura Payan-Bravo, Sara Fontalva, Xenia Penate, Ildefonso Cases, Jose Antonio Guerrero-Martinez, Yerma Pareja-Sanchez, Yosu Odriozola-Gil, Esther Lara, Silvia Jimeno-Gonzalez, Carles Sune, Mari Cruz Munoz-Centeno, Jose C. Reyes, Sebastian Chavez
Summary: The study demonstrates that perturbations in prefoldin lead to transcriptional alterations in the human genome, particularly affecting splicing and expression of long genes with a high number of introns.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Christophe Rachez, Rachel Legendre, Mickael Costallat, Hugo Varet, Jia Yi, Etienne Kornobis, Christian Muchardt
Summary: HP1 proteins, known for marking heterochromatin and gene silencing, are also RNA-binding proteins. HP1 gamma, in particular, is targeted to hexameric RNA motifs and SINE transposable elements, tethering unspliced pre-mRNA to chromatin through intronic regions and limiting the usage of intronic cryptic splice sites during transcription. This reveals new insights into the relationship between chromatin and co-transcriptional splicing.
Review
Oncology
Sunkyung Choi, Namjoon Cho, Eun-Mi Kim, Kee K. Kim
Summary: Alternative pre-mRNA splicing plays a critical role in generating multiple mRNA and increasing protein diversity. Specific splicing isoforms have been found to be important in cellular processes, particularly in regulating cell numbers. Abnormal expression of splicing isoforms and factors, as well as disruptions in splicing caused by genetic mutations, are implicated in cancer development and progression. Alternative splicing has potential as a therapeutic target for cancer.
CANCER CELL INTERNATIONAL
(2023)