Toggle Main Menu Toggle Search

Open Access padlockePrints

Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement

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.

Publication metadata

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


DOI: 10.1038/s41598-019-41483-9

PubMed id: 30911037


Altmetrics provided by Altmetric


Funder referenceFunder name
203105/Z/16/ZWellcome Trust
CGThe Drinkaware Trust
CGLeica Biosystems Newcastle Ltd (Novocastra Laboratories)
CGLeica Biosystems Newcastle Ltd (Novocastra Laboratories)
Medical Research Council (MRC) Centre for Translational Research in Neuromuscular Disease
Lily Foundation
National Institute of Neurological Disorders
UK NHS Highly Specialised Service for Rare Mitochondial Disorders of Adults and Children