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Lookup NU author(s): Ruth Glasgow, Dr Steven Hardy, Gavin Falkous, Dr Langping He, Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s). Primary mitochondrial dysfunction is an under-appreciated cause of cardiomyopathy, especially when cardiac symptoms are the unique or prevalent manifestation of disease. Here, we report an unusual presentation of mitochondrial cardiomyopathy, with dilated phenotype and pathologic evidence of biventricular fibro-adipose replacement, in a 33-year old woman who underwent cardiac transplant. Whole exome sequencing revealed two novel compound heterozygous variants in the TSFM gene, coding for the mitochondrial translation elongation factor EF-Ts. This protein participates in the elongation step of mitochondrial translation by binding and stabilizing the translation elongation factor Tu (EF-Tu). Bioinformatics analysis predicted a destabilization of the EF-Ts variants complex with EF-Tu, in agreement with the dramatic steady-state level reduction of both proteins in the clinically affected myocardium, which demonstrated a combined respiratory chain enzyme deficiency. In patient fibroblasts, the decrease of EF-Ts was paralleled by up-regulation of EF-Tu and induction of genes involved in mitochondrial biogenesis, along with increased expression of respiratory chain subunits and normal oxygen consumption rate. Our report extends the current picture of morphologic phenotypes associated with mitochondrial cardiomyopathies and confirms the heart as a main target of TSFM dysfunction. The compensatory response detected in patient fibroblasts might explain the tissue-specific expression of TSFM-associated disease.
Author(s): Perli E, Pisano A, Glasgow RIC, Carbo M, Hardy SA, Falkous G, He L, Cerbelli B, Pignataro MG, Zacara E, Re F, Della Monica PL, Morea V, Bonnen PE, Taylor RW, d'Amati G, Giordano C
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2019
Volume: 9
Issue: 1
Online publication date: 25/03/2019
Acceptance date: 07/03/2019
Date deposited: 10/04/2019
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41598-019-41483-9
DOI: 10.1038/s41598-019-41483-9
PubMed id: 30911037
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