A Novel Mutation of the <i>TAZ</i> Gene in Barth Syndrome: Acute Exacerbation after Contrast-Dye Injection

Kim, Jun Seok; Kwon, Bo Sang; Bae, Eun Jung; Noh, Chung Il; Seong, Moon Woo; Park, Sung Sup

doi:10.3346/jkms.2013.28.5.784

Cited by 5 publications

(2 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, chronic β‐adrenergic activation can be detrimental and studies have linked it to DCM, heart failure, and early mortality (Dash et al, ; Grimm and Brown, ). Thus, it is possible that improving SERCA function in Taz KD mice may lessen the need for β‐adrenergic stimulation and thus improve the physiological outcome in these mice and perhaps in Barth syndrome patients who are often prescribed beta blockers such as carvedilol (Kim et al, ).…”

Section: Discussionmentioning

confidence: 99%

SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin‐deficient mice

et al. 2019

View full text Add to dashboard Cite

The sarco/endoplasmic reticulum Ca 2+ ‐ATPase (SERCA) is imperative for normal cardiac function regulating both muscle relaxation and contractility. SERCA2a is the predominant isoform in cardiac muscles and is inhibited by phospholamban (PLN). Under conditions of oxidative stress, SERCA2a may also be impaired by tyrosine nitration. Tafazzin (Taz) is a mitochondrial‐specific transacylase that regulates mature cardiolipin (CL) formation, and its absence leads to mitochondrial dysfunction and excessive production of reactive oxygen/nitrogen species (ROS/RNS). In the present study, we examined SERCA function, SERCA2a tyrosine nitration, and PLN expression/phosphorylation in left ventricles (LV) obtained from young (3‐5 months) and old (10‐12 months) wild‐type (WT) and Taz knockdown (Taz KD ) male mice. These mice are a mouse model for Barth syndrome, which is characterized by mitochondrial dysfunction, excessive ROS/RNS production, and dilated cardiomyopathy (DCM). Here, we show that maximal SERCA activity was impaired in both young and old Taz KD LV, a result that correlated with elevated SERCA2a tyrosine nitration. In addition PLN protein was decreased, and its phosphorylation was increased in Taz KD LV compared with control, which suggests that PLN may not contribute to the impairments in SERCA function. These changes in expression and phosphorylation of PLN may be an adaptive response aimed to improve SERCA function in Taz KD mice. Nonetheless, we demonstrate for the first time that SERCA function is impaired in LVs obtained from young and old Taz KD mice likely due to elevated ROS/RNS production. Future studies should determine whether improving SERCA function can improve cardiac contractility and pathology in Taz KD mice.

show abstract

Section: Discussionmentioning

confidence: 99%

SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin‐deficient mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“… 11) 12) In Korea, one patient with BTHS was recently identified; he died after contrast dye injection for computed tomographic angiography. 13) Our patient had a novel de novo mutation that was a hemizygous in-frame deletion in his TAZ gene, c.725_751del (p.Pro242_Glu250del), which was not inherited from his mother. To the best of our knowledge, this is the first reported case of a BTHS patient with a de novo mutation in Korea.…”

Section: Discussionmentioning

confidence: 87%

Identification of a Novel De Novo Mutation of the TAZ Gene in a Korean Patient with Barth Syndrome

Yoo

Kim

Son

et al. 2016

J Cardiovasc Ultrasound

Self Cite

View full text Add to dashboard Cite

Barth syndrome (BTHS) is a rare genetic disorder characterized by various types of cardiomyopathy, neutropenia, failure to thrive, skeletal myopathy, and 3-methylglutaconic aciduria. BTHS is caused by loss-of-function mutations in the tafazzin (TAZ) gene located on chromosome Xq28, leading to cardiolipin deficiency. We report a 13-month-old boy with BTHS who had a novel de novo mutation in the TAZ gene. To the best of our knowledge, this is the first reported case of a BTHS patient with a de novo mutation in Korea. This report will contribute towards expanding the knowledge on the mutation spectrum of the TAZ gene in BTHS.

show abstract

Mis-sesnse mutations in Tafazzin (TAZ) that escort to mild clinical symptoms of Barth syndrome is owed to the minimal inhibitory effect of the mutations on the enzyme function: In-silico evidence

Debnath¹,

Addya²

2014

Interdiscip Sci Comput Life Sci

View full text Add to dashboard Cite

Tafazzin (EC 2.3.1.23) is a Phospholipid Transacylase involved in Cardiolipin remodeling on mitochondrial membrane and coded by TAZ gene (Cytogenetic Location: Xq28) in human. Its mutations cause Barth syndrome (MIM ID: #302060)/3-Methyl Glutaconyl Aciduria Type II, an inborn error of metabolism often leading to foetal or infantile fatality. Nevertheless, some mis-sense mutations result in mild clinical symptoms. To evaluate the rationale of mild symptoms and for an insight of Tafazzin active site, sequence based and structure based ramifications of wild and mutant Tafazzins were compared in-silico. Sequence based domain predictions, surface accessibilities on substitution & conserved catalytic sites with statistical drifts, as well as thermal stability changes for the mutations and the interaction analysis of Tafazzin were performed. Crystal structure of Tafazzin is not yet resolved experimentally, therefore 3D coordinates of Tafazzin and its mutants were spawned through homology modeling. Energetically minimized and structurally validated models were used for comparative docking simulations. We analyzed active site geometry of the models in addition to calculating overall substrate binding efficiencies for each of the enzyme-ligand complex deduced from binding energies instead of comparing only the docking scores. Also, individual binding energies of catalytic residues on conserved HX4D motif of Acyltransferase superfamily present in Tafazzins were estimated. This work elucidates the basis of mild symptoms in patients with mis-sense mutations, identifies the most pathogenic mutant among others in the study and also divulges the critical role of HX4D domain towards successful transacylation by Taffazin. The in-silico observations are in complete agreement with clinical findings reported for the patients with mutations.

show abstract

A Novel Mutation of the TAZ Gene in Barth Syndrome: Acute Exacerbation after Contrast-Dye Injection

Cited by 5 publications

References 8 publications

SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin‐deficient mice

SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin‐deficient mice

Identification of a Novel De Novo Mutation of the TAZ Gene in a Korean Patient with Barth Syndrome

Mis-sesnse mutations in Tafazzin (TAZ) that escort to mild clinical symptoms of Barth syndrome is owed to the minimal inhibitory effect of the mutations on the enzyme function: In-silico evidence

Contact Info

Product

Resources

About