Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings
Tóm tắt
TSFM is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery. Impaired mitochondrial translation is responsible for neurodegenerative disorders characterized by multiple respiratory chain complex defects, multisystemic involvement, and neuroradiological features of Leigh-like syndrome. With the use of a next-generation sequencing (NGS)–based multigene panel for mitochondrial disorders, we identified the novel TSFM homozygous variant c.547G>A (p.Gly183Ser) in a 5-year-old boy with infantile early onset encephalocardiomyopathy, sensorineural hearing loss, and peculiar partially reversible neuroimaging features. Our findings expand the phenotypic spectrum of TSFM-related encephalopathy, offering new insights into the natural history of brain involvement and suggesting that TSFM should be investigated in pediatric mitochondrial disorders with distinctive neurologic and cardiac involvement.
Tài liệu tham khảo
Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, Suomalainen A, Thorburn DR, Zeviani M, Turnbull DM (2016) Mitochondrial diseases. Nat Rev Dis Primers 2:16080. https://doi.org/10.1038/nrdp.2016.80
Boczonadi V, Horvath R (2014) Mitochondria: impaired mitochondrial translation in human disease. Int J Biochem Cell Biol 48:77–84. https://doi.org/10.1016/j.biocel.2013.12.011
Ahola S, Isohanni P, Euro L, Brilhante V, Palotie A, Pihko H, Lönnqvist T, Lehtonen T, Laine J, Tyynismaa H, Suomalainen A (2014) Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy. Neurology 83(8):743–751. https://doi.org/10.1212/WNL.0000000000000716
Morrison FS, Locke JM, Wood AR, Tuke M, Pasko D, Murray A, Frayling T, Harries LW (2013) The splice site variant rs11078928 may be associated with a genotype-dependent alteration in expression of GSDMB transcripts. BMC Genomics 14:627. https://doi.org/10.1186/1471-2164-14-627
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL (2015) ACMG laboratory quality assurance committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. https://doi.org/10.1038/gim.2015.30
Lake NJ, Compton AG, Rahman S, Thorburn DR (2016) Leigh syndrome: one disorder, more than 75 monogenic causes. Ann Neurol 79(2):190–203. https://doi.org/10.1002/ana.24551
Jeppesen MG, Navratil T, Spremulli LL, Nyborg J (2005) Crystal structure of the bovine mitochondrial elongation factor Tu.Ts complex. J Biol Chem 280:5071–5081
Smeitink JA, Elpeleg O, Antonicka H, Diepstra H, Saada A, Smits P, Sasarman F, Vriend G, Jacob-Hirsch J, Shaag A, Rechavi G, Welling B, Horst J, Rodenburg RJ, van den Heuvel B, Shoubridge EA (2006) Distinct clinical phenotypes associated with a mutation in the mitochondrialtranslation elongation factor EFTs. Am J Hum Genet 79(5):869–877
Emperador S, Bayona-Bafaluy MP, Fernández-Marmiesse A, Pineda M, Felgueroso B, López-Gallardo E, Artuch R, Roca I, Ruiz-Pesini E, Couce ML, Montoya J (2016) Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and non obstructive cardiomyopathy. Eur J Hum Genet 25(1):153–156. https://doi.org/10.1038/ejhg.2016.124
Traschütz A, Hayer SN, Bender B, Schöls L, Biskup S, Synofzik M (2018) TSFM mutations cause a complex hyperkinetic movement disorder with strong relief by cannabinoids. Parkinsonism Relat Disord 60:176–178. https://doi.org/10.1016/j.parkreldis.2018.09.031
Vedrenne V, Galmiche L, Chretien D, de Lonlay P, Munnich A, Rötig A (2012) Mutation in the mitochondrial translation elongation factor EFTs results in severe infantile liver failure. J Hepatol 56(1):294–297. https://doi.org/10.1016/j.jhep.2011.06.014
Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK (2012) Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing. Sci Transl Med 4(118):118ra10. https://doi.org/10.1126/scitranslmed.3003310
Giribaldi G, Doria-Lamba L, Biancheri R, Severino M, Rossi A, Santorelli FM, Schiaffino C, Caruso U, Piemonte F, Bruno C (2012) Intermittent-relapsing pyruvate dehydrogenasecomplexdeficiency: a case with clinical, biochemical, and neuroradiological reversibility. Dev Med Child Neurol 54(5):472–476. https://doi.org/10.1111/j.1469-8749.2011.04151.x
Sasai H, Shimozawa N, Asano T, Kawamoto N, Yamamoto T, Kimura T, Kawamoto M, Matsui E, Fukao T (2015) Successive MRI findings of reversible cerebral white matter lesions in patient with cystathionine β-synthase deficiency. Tohoku J Exp Med 237(4):323–327. https://doi.org/10.1620/tjem.237.323
Kozić DB, Petrović I, Svetel M, Pekmezović T, Ragaji A, Kostić VS (2014) Reversible lesions in the brain parenchyma in Wilson’s disease confirmed by magneticresonance imaging: earlier administration of chelating therapy can reduce the damage to the brain. Neural Regen Res 9(21):1912–1916. https://doi.org/10.4103/1673-5374.145360
El-Hattab AW, Adesina AM, Jones J, Scaglia F (2015) MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab 116(1–2):4–12. https://doi.org/10.1016/j.ymgme.2015.06.004
Iizuka T, Sakai F, Suzuki N, Hata T, Tsukahara S, Fukuda M, Takiyama Y (2002) Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome. Neurology 59(6):816–824
Sakai S, Osaki M, Hidaka M, Kimura S, Ohya Y, Ago T, Kitazono T, Arakawa S (2018) Association between stroke-like episodes and neuronal hyperexcitability in MELAS with m.3243A>G: a case report. eNeurologicalSci. 12:39–41. https://doi.org/10.1016/j.ensci.2018.08.003 eCollection 2018 Sep.