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Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
Barth syndrome, initially described as X-linked cardioskeletal myopathy with abnormal mitochondria and neutropenia, typically presents in male infants as HF associated with neutropenia and 3-methylglutaconic aciduria. The genetic basis of Barth syndrome is mutations in the gene tafazzin (TAZ), which encodes the tafazzin protein, an acyltransferase. Mutations in TAZ result in a wide range of findings, including DCM, HCM, endocardial fibroelastosis, or left ventricular noncompaction. Arrhythmias are also frequent in these patients, and syncope or sudden death, acidosis, or infectious complications occur.24
Cardiac and cardiovascular disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Endocardial fibroelastosis may be secondary to acquired myocarditis or may accompany other congenital heart defects; idiopathic fibroelastosis should be accepted as the diagnosis only with autopsy or biopsy evidence. Some cases may result from systemic carnitine deficiency. A thorough study from Toronto found a recurrence risk of 3.8% in sibs, rather higher than expected from the incidence of the disorder. It is possible that a small subgroup follows autosomal recessive inheritance but, if it exists, it cannot at present be distinguished from the majority and may represent an underlying metabolic disorder. Remember that the cardiac phenotype of the X-linked Barth syndrome can manifest as endocardial fibroelastosis, not always as a simple (i.e. typical) cardiomyopathy.
Mitochondrial Dysfunction and Barth Syndrome
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Arianna F. Anzmann, Steven M. Claypool, Hilary Vernon
In 1980, Barth et al. described a novel X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leukocytes, at a Neuromuscular Disease Symposium held at Erasmus University1. Three years after this preliminary communication, Barth et al. reported a large Dutch family with cardiomyopathy, skeletal myopathy, neutropenia, and high infant mortality due to infection or cardiac failure2. These clinical characteristics have since become the cardinal features of what is now known as Barth syndrome (BTHS, MIM#302060) (Figure 1)3–6. The incidence of BTHS is estimated to be about 1/300,000–400,000 live births, with fewer than 500 individuals worldwide included in the BTHS Registry & Repository. There is no known racial or ethnic predilection7,8.
‘You-on-a-chip’ for precision medicine
Published in Expert Review of Precision Medicine and Drug Development, 2018
The promise for rare disease tissue modeling and therapeutic testing is highlighted by work recreating the pediatric mitochondrial cardiomyopathy Barth syndrome, which is caused by a mutation in the gene encoding the protein tafazzin (TAZ), on a tissue chip [97]. iPSC-derived cardiomyocytes were created from two patient donors and seeded onto muscular thin films (MTFs) – flexible films that twitch in a quantifiable manner as the cells beat together [98]. Researchers used the MTFs to compare Barth syndrome sarcomere organization, functional twitching, and peak systolic stress, so uncovering insights into disease pathology. In addition, they used genome edited iPSCs and modified RNA (modRNA) genetic approaches to show that induction of the genetic TAZ mutation caused Barth-like phenotypes in resulting cardiac tissues, which could be rescued upon genetic correction. These kinds of approach hold much promise for understanding and potentially treating other diseases, including mitochondrial disorders and cystic fibrosis.
Significant expression of tafazzin (TAZ) protein in colon cancer cells and its downregulation by radiation
Published in International Journal of Radiation Biology, 2018
Surajit Pathak, Antara Banerjee, Wen-Jian Meng, Suman Kumar Nandy, Madhumala Gopinath, Xiao-Feng Sun
Many transcriptional factors have shown to interact with TAZ and activity of TAZ depends on its binding to different transcription factors (Wang et al. 2008). The present study is a comparative data of how the three genes, Livin, MAC30 and FXYD3 interact with TAZ/WWTR1. In our previous papers on TAZ protein, which is generally responsible for barth syndrome, upregulated in colorectal cancer (Pathak et al. 2014), we have showed the function and overexpression of these genes individually and its essential role played in colorectal cancers. Functional subunits of Livin and TAZ, FXYD3 and TAZ with strong binding of TAZ and Livin with TEAD, TAZ and MAC30 which is specific not only in colon cancer but its function in initiating lymph node metastasis in colorectal cancer was also reported. TAZ and FXYD3 role in germline sex determination as well its ability to directly influence endogenous oocytes was reason for initiating the study. The relationship was further established through the PCR studies which showed that treatment of HCT15 cell lines with 9-fluorenone, a known Hippo pathway inhibitor of TAZ, significantly decreased the levels of not only TAZ but also the level of Livin. This shows that the network regulation of Hippo pathway is regulated by not only TAZ but also certain unknown regulators like Livin, that can be further investigated upon.
Fetal hydrops – a review and a clinical approach to identifying the cause
Published in Expert Opinion on Orphan Drugs, 2020
Esther Dempsey, Tessa Homfray, John M Simpson, Steve Jeffery, Sahar Mansour, Pia Ostergaard
Barth Syndrome is an X-linked disorder of mitochondrial function and stability caused by mutations in TAZ [85]. Clinically the condition results in a dilated cardiomyopathy with endocardial fibroelastosis, which can lead to hydrops antenatally [86]. On fetal echocardiography, crypts are characteristically seen in the apex and free wall [82]. Those that survive may show growth retardation, proximal skeletal myopathy, neutropenia and organic aciduria [85,87].