TAZ mutations are implicated in Barth syndrome, an underdiagnosed and devastating disease that primarily affects male pediatric patients with a broad spectrum of disease pathologies that impact the cardiovascular, neuromuscular, metabolic, and hematologic systems.
Our observation provides novel insights into the temporal appearance of 3-MGA-uria in TMEM70 and TAZ mutations (Barth syndrome) and focus the importance of multidisciplinary management and careful evaluation of family history and red flag signs for phenocopies in infantile onset cardiomyopathies.
Our objective was to review published data from the TAZKD mouse to determine its contributions to our pathogenetic understanding of, and potential treatment strategies for, Barth syndrome.
Mutations in Tafazzin lead to Barth syndrome (BTHS), a metabolic and neuromuscular disorder that primarily affects the heart, muscles, and immune system.
To develop a clinically relevant gene therapy to restore tafazzin function and treat BTHS, three different adeno-associated virus serotype 9 vectors were tested and compared to identify the optimal promoter-cytomegalovirus (CMV), desmin (Des), or a native tafazzin promoter (Taz)-for TAZ expression following intravenous administration of 1 × 10<sup>13</sup> vector genomes/kilogram to a mouse model of BTHS as either neonates (1-2 days of age) or adults (3 months of age).
Barth syndrome (BTHS) is an X-linked disorder caused by defects in TAZ with key clinical features including cardiomyopathy, neutropenia and skeletal myopathy.
We tested COPAL on complexome profiles from control mitochondria and from Barth syndrome (BTHS) mitochondria, which have a mutation in tafazzin gene that is involved in remodeling the inner mitochondrial membrane phospholipid cardiolipin.
These peptides are not located within the predicted enzymatic clefts of TAZ, implying that some BTHS disease causing mutations may affect mitochondrial localization without affecting transacylase activity.
To quantitatively assess possible specific roles of peroxidation and hydrolysis of mitochondrial CL, we performed comparative studies of CL modifications using an animal model of Barth syndrome where deficiency of CL reacylation (Tafazzin [Taz] deficiency) was associated exclusively with the accumulation of mCLs (but not CLox).
Here we determine using high-resolution <sup>31</sup>P nuclear magnetic resonance with cryoprobe technology the fundamental phospholipid composition, including the major but oxidation-labile plasmalogens, in the tafazzin-knockdown (TAZ-KD) mouse heart as a model of Barth syndrome.
Overall, insights from analyzing the impact of TAZ mutations on the mitochondrial complexome provided a better understanding of the resulting functional and structural consequences and thus the pathological mechanisms leading to Barth syndrome.
<b>Aim:</b> Tafazzin knockdown (TazKD) in mice is widely used to create an experimental model of Barth syndrome (BTHS) that exhibits dilated cardiomyopathy and impaired exercise capacity.
In this study, we analyzed what relationship, if any, exists between TAZ and MLCL AT-1 with regard to CL remodeling and whether transfection of BTHS lymphoblasts with an <i>MLCL AT-1</i> expression construct improves mitochondrial respiratory function.
Barth Syndrome (BTHS) is a rare X-linked genetic disease in which the specific biochemical deficit is a reduction in the mitochondrial phospholipid cardiolipin (CL) as a result of a mutation in the CL transacylase tafazzin.
Although tafazzin-knockdown mouse is a reasonable model for the study of Barth syndrome pathophysiology, it is not a precise simulacrum of the human condition.