<italic>TTN</italic>基因突变致儿童扩张型心肌病的研究进展

doi:10.7499/j.issn.1008-8830.2208163

Abstract
Figure/Table
References(32)
Related Citation (15)
Read Tracking
Download Tracking

Download: PDF (553 KB) HTML
Export: BibTeX | EndNote (RIS) Supporting Info

Abstract The mutations of TTN gene that encodes titin are the most common mutation type among the genetic causes of dilated cardiomyopathy (DCM). This article reviews the worldwide studies on potential molecular pathogenesis (transcription, post-translational modification, etc.), clinical phenotypes, and gene therapies of pediatric DCM caused by TTN mutations, with the hope of providing a reference for the precision treatment of pediatric DCM caused by TTN mutations.

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	ZHENG Kui
	LOU Mei-Na

Key words： Dilated cardiomyopathy TTN gene Titin Treatment Child

Received: 26 August 2022

Cite this article:

ZHENG Kui,LOU Mei-Na. Recent studies on dilated cardiomyopathy caused by TTN mutations in children[J]. CJCP, 2023, 25(2): 217-222.

URL:

http://www.zgddek.com/EN/10.7499/j.issn.1008-8830.2208163 OR http://www.zgddek.com/EN/Y2023/V25/I2/217

	Wang Y, Han B, Fan Y, et al. Next-generation sequencing reveals novel genetic variants for dilated cardiomyopathy in pediatric Chinese patients[J]. Pediatr Cardiol, 2022, 43(1): 110-120. PMID: 34350506. DOI: 10.1007/s00246-021-02698-8.
	2 郑奎, 张英谦, 刘露, 等. 32例儿童心肌病基因检测与临床特征分析[J]. 临床心血管病杂志, 2022, 38(7): 566-571. DOI: 10.13201/j.issn.1001-1439.2022.07.010.
	Azad A, Poloni G, Sontayananon N, et al. The giant titin: how to evaluate its role in cardiomyopathies[J]. J Muscle Res Cell Motil, 2019, 40(2): 159-167. PMID: 31147888. PMCID: PMC6726704. DOI: 10.1007/s10974-019-09518-w.
	Tharp CA, Haywood ME, Sbaizero O, et al. The giant protein titin's role in cardiomyopathy: genetic, transcriptional, and post-translational modifications of TTN and their contribution to cardiac disease[J]. Front Physiol, 2019, 10: 1436. PMID: 31849696. PMCID: PMC6892752. DOI: 10.3389/fphys.2019.01436.
	Liu G, Yang Z, Chen W, et al. Novel missense variant in TTN cosegregating with familial atrioventricular block[J]. Eur J Med Genet, 2020, 63(3): 103752. PMID: 31470098. DOI: 10.1016/j.ejmg.2019.103752.
	6 王晶, 徐文峰, 陈頔, 等. 治疗45外显子跳跃突变杜氏肌营养不良症的药物——Casimersen[J]. 临床药物治疗杂志, 2022, 20(5): 17-20. DOI: 10.3969/j.issn.1672-3384.2022.05.004.
	Loescher CM, Hobbach AJ, Linke WA. Titin (TTN): from molecule to modifications, mechanics, and medical significance[J]. Cardiovasc Res, 2022, 118(14): 2903-2918. PMID: 34662387. PMCID: PMC9648829. DOI: 10.1093/cvr/cvab328.
	Gerull B. The rapidly evolving role of titin in cardiac physiology and cardiomyopathy[J]. Can J Cardiol, 2015, 31(11): 1351-1359. PMID: 26518445. DOI: 10.1016/j.cjca.2015.08.016.
	Santiago CF, Huttner IG, Fatkin D. Mechanisms of TTN tv-related dilated cardiomyopathy: insights from zebrafish models[J]. J Cardiovasc Dev Dis, 2021, 8(2): 10. PMID: 33504111. PMCID: PMC7912658. DOI: 10.3390/jcdd8020010.
	Kellermayer D, Smith JE, Granzier H. Titin mutations and muscle disease[J]. Pflugers Arch, 2019, 471(5): 673-682. PMID: 30919088. PMCID: PMC6481931. DOI: 10.1007/s00424-019-02272-5.
	Tharp C, Mestroni L, Taylor M. Modifications of titin contribute to the progression of cardiomyopathy and represent a therapeutic target for treatment of heart failure[J]. J Clin Med, 2020, 9(9): 2770. PMID: 32859027. PMCID: PMC7564493. DOI: 10.3390/jcm9092770.
	Dai G, Pu Z, Cheng X, et al. Whole-exome sequencing reveals novel genetic variation for dilated cardiomyopathy in pediatric Chinese patients[J]. Pediatr Cardiol, 2019, 40(5): 950-957. PMID: 30993396.DOI: 10.1007/s00246-019-02096-1.
	Khan RS, Pahl E, Dellefave-Castillo L, et al. Genotype and cardiac outcomes in pediatric dilated cardiomyopathy[J]. J Am Heart Assoc, 2022, 11(1): e022854. PMID: 34935411.PMCID: PMC9075202.DOI: 10.1161/JAHA.121.022854.
	Akinrinade O, Heli? T, Lekanne Deprez RH, et al. Relevance of titin missense and non-frameshifting insertions/deletions variants in dilated cardiomyopathy[J]. Sci Rep, 2019, 9(1): 4093. PMID: 30858397. PMCID: PMC6412046. DOI: 10.1038/s41598-019-39911-x.
	15 李发有, 范洁. 肌联蛋白基因截断突变致家族性扩张型心肌病的研究进展[J]. 中国循环杂志, 2015, 30(7): 715-717. DOI: 10.3969/j.issn.1000-3614.2015.07.025.
	Fatkin D, Huttner IG. Titin-truncating mutations in dilated cardiomyopathy: the long and short of it[J]. Curr Opin Cardiol, 2017, 32(3): 232-238. PMID: 28151760. DOI: 10.1097/HCO.0000000000000382.
	Vikhorev PG, Vikhoreva NN, Yeung W, et al. Titin-truncating mutations associated with dilated cardiomyopathy alter length-dependent activation and its modulation via phosphorylation[J]. Cardiovasc Res, 2022, 118(1): 241-253. PMID: 33135063. PMCID: PMC8752363. DOI: 10.1093/cvr/cvaa316.
	Fomin A, G?rtner A, Cyganek L, et al. Truncated titin proteins and titin haploinsufficiency are targets for functional recovery in human cardiomyopathy due to TTN mutations[J]. Sci Transl Med, 2021, 13(618): eabd3079. PMID: 34731013. DOI: 10.1126/scitranslmed.abd3079.
	Biquand A, Spinozzi S, Tonino P, et al. Titin M-line insertion sequence 7 is required for proper cardiac function in mice[J]. J Cell Sci, 2021, 134(18): jcs258684. PMID: 34401916. PMCID: PMC8466004. DOI: 10.1242/jcs.258684.
	Zhu C, Yin Z, Ren J, et al. RBM20 is an essential factor for thyroid hormone-regulated titin isoform transition[J]. J Mol Cell Biol, 2015, 7(1): 88-90. PMID: 25573899. PMCID: PMC4400401. DOI: 10.1093/jmcb/mjv002.
	Hidalgo C, Hudson B, Bogomolovas J, et al. PKC phosphorylation of titin's PEVK element: a novel and conserved pathway for modulating myocardial stiffness[J]. Circ Res, 2009, 105(7): 631-638, 17 p following 638. PMID: 19679839. PMCID: PMC2764991. DOI: 10.1161/CIRCRESAHA.109.198465.
	Schafer S, de Marvao A, Adami E, et al. Titin-truncating variants affect heart function in disease cohorts and the general population[J]. Nat Genet, 2017, 49(1): 46-53. PMID: 27869827. PMCID: PMC5201198. DOI: 10.1038/ng.3719.
	Adams M, Fleming JR, Riehle E, et al. Scalable, non-denaturing purification of phosphoproteins using Ga3+-IMAC: N2A and M1M2 titin components as study case[J]. Protein J, 2019, 38(2): 181-189. PMID: 30719619. DOI: 10.1007/s10930-019-09815-w.
	Verdonschot JAJ, Hazebroek MR, Derks KWJ, et al. Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias[J]. Eur Heart J, 2018, 39(10): 864-873. PMID: 29377983. DOI: 10.1093/eurheartj/ehx808.
	Linschoten M, Teske AJ, Baas AF, et al. Truncating titin (TTN) variants in chemotherapy-induced cardiomyopathy[J]. J Card Fail, 2017, 23(6): 476-479. PMID: 28315399. DOI: 10.1016/j.cardfail.2017.03.003.
	Ware JS, Cook SA. Role of titin in cardiomyopathy: from DNA variants to patient stratification[J]. Nat Rev Cardiol, 2018, 15(4): 241-252. PMID: 29238064. DOI: 10.1038/nrcardio.2017.190.
	Franaszczyk M, Chmielewski P, Truszkowska G, et al. Titin truncating variants in dilated cardiomyopathy: prevalence and genotype-phenotype correlations[J]. PLoS One, 2017, 12(1): e0169007. PMID: 28045975. PMCID: PMC5207678. DOI: 10.1371/journal.pone.0169007.
	Ahlberg G, Refsgaard L, Lundegaard PR, et al. Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation[J]. Nat Commun, 2018, 9(1): 4316. PMID: 30333491. PMCID: PMC6193003. DOI: 10.1038/s41467-018-06618-y.
	Enriquez A, Liang J, Smietana J, et al. Substrate characterization and outcomes of ventricular tachycardia ablation in TTN (titin) cardiomyopathy: a multicenter study[J]. Circ Arrhythm Electrophysiol, 2021, 14(9): e010006. PMID: 34315225. DOI: 10.1161/CIRCEP.121.010006.
	Pe?a-Pe?a ML, Ochoa JP, Barriales-Villa R, et al. Prognostic implications of pathogenic truncating variants in the TTN gene[J]. Int J Cardiol, 2020, 316: 180-183. PMID: 32371228. DOI: 10.1016/j.ijcard.2020.04.086.
	Gramlich M, Pane LS, Zhou Q, et al. Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy[J]. EMBO Mol Med, 2015, 7(5): 562-576. PMID: 25759365. PMCID: PMC4492817. DOI: 10.15252/emmm.201505047.
	Hahn JK, Neupane B, Pradhan K, et al. The assembly and evaluation of antisense oligonucleotides applied in exon skipping for titin-based mutations in dilated cardiomyopathy[J]. J Mol Cell Cardiol, 2019, 131: 12-19. PMID: 30998980. DOI: 10.1016/j.yjmcc.2019.04.014.