TSFM, also known as mitochondrial Ts translation elongation factor, is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery [2]. By forming a complex with mitochondrial Tu translation elongation factor (TUFM), TSFM participates in mitochondrial protein translation, which is crucial for normal cell function and is associated with various biological processes related to mitochondrial function [3].

Mutations in TSFM have been linked to multiple disorders. For instance, in a 5-year-old boy, a novel homozygous TSFM variant c.547G>A (p.Gly183Ser) was identified, causing infantile early-onset encephalocardiomyopathy, sensorineural hearing loss, and peculiar partially reversible neuroimaging features, expanding the phenotypic spectrum of TSFM-related encephalopathy [2]. In a 3-year-old female, compound heterozygous variants in TSFM led to hypertrophic cardiomyopathy and lactic acidosis, with cardiac and skeletal muscles biopsies showing mitochondrial hyperplasia and decreased complex IV activity [5]. Also, a 33-year-old woman with mitochondrial cardiomyopathy, presenting with dilated phenotype and pathologic evidence of biventricular fibro-adipose replacement, had two novel compound heterozygous variants in TSFM [6]. Additionally, TSFM mutations have been associated with a complex hyperkinetic movement disorder that can be strongly relieved by cannabinoids [1], as well as early-onset complex chorea without basal ganglia lesions [4]. Bioinformatics analysis also uncovered the possibility of TSFM involvement in cardiomyopathy and cancer development [3].

In conclusion, TSFM is vital for mitochondrial translational processes. Research on TSFM mutations in various patient cases has revealed its significance in multiple disease areas, including neurodegenerative, cardiac, and potentially cancer-related disorders. Understanding TSFM's functions and its role in these diseases may provide insights into disease mechanisms and potential treatment strategies.

References:

1. Traschütz, Andreas, Hayer, Stefanie N, Bender, Benjamin, Biskup, Saskia, Synofzik, Matthis. 2018. TSFM mutations cause a complex hyperkinetic movement disorder with strong relief by cannabinoids. In Parkinsonism & related disorders, 60, 176-178. doi:10.1016/j.parkreldis.2018.09.031. https://pubmed.ncbi.nlm.nih.gov/30297209/

2. Scala, Marcello, Brigati, Giorgia, Fiorillo, Chiara, Minetti, Carlo, Santorelli, F M. 2019. Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings. In Neurogenetics, 20, 165-172. doi:10.1007/s10048-019-00582-5. https://pubmed.ncbi.nlm.nih.gov/31267352/

3. Li, Xiao-Yun, Zhou, Gui-Feng, Xie, Xiong-Yong, Wang, Lu, Chen, Guo-Jun. 2024. Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells. In Molecular biology reports, 51, 484. doi:10.1007/s11033-024-09426-4. https://pubmed.ncbi.nlm.nih.gov/38578353/

4. van Riesen, Anne K, Biskup, Saskia, Kühn, Andrea A, Kaindl, Angela M, van Riesen, Christoph. 2021. Novel Mutation in the TSFM Gene Causes an Early-Onset Complex Chorea without Basal Ganglia Lesions. In Movement disorders clinical practice, 8, 453-455. doi:10.1002/mdc3.13144. https://pubmed.ncbi.nlm.nih.gov/33816677/

5. Yang, Jamie O, Shaybekyan, Hapet, Zhao, Yan, Nelson, Stanley F, Touma, Marlin. 2022. Case Report: Whole Exome Sequencing Identifies Compound Heterozygous Variants in TSFM Gene Causing Juvenile Hypertrophic Cardiomyopathy. In Frontiers in cardiovascular medicine, 8, 798985. doi:10.3389/fcvm.2021.798985. https://pubmed.ncbi.nlm.nih.gov/35071363/

6. Perli, Elena, Pisano, Annalinda, Glasgow, Ruth I C, d'Amati, Giulia, Giordano, Carla. 2019. Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement. In Scientific reports, 9, 5108. doi:10.1038/s41598-019-41483-9. https://pubmed.ncbi.nlm.nih.gov/30911037/