Volume 27, Issue 2 And 3 (3-2023)                   IBJ 2023, 27(2 And 3): 146-151 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Khakzad M, Shahbazi Z, Naderi M, Karimipour M. A de novo TINF2, R282C Mutation in a Case of Dyskeratosis Congenital Founded by Next-Generation Sequencing. IBJ 2023; 27 (2 and 3) :146-151
URL: http://ibj.pasteur.ac.ir/article-1-3783-en.html
Introduction: Dyskeratosis congenita, an inherited and rare disease prevalent in males, is clinically manifested by reticulate hyperpigmentation, nail dystrophy, and leukoplakia. DC is associated with the increased risk of malignancy and other potentially lethal complications such as bone marrow failure, as well as lung and liver diseases. Mutations in 19 genes were found to be correlated with DC. Herein, we report a 12-year-old boy carrying a de novo mutation in TINF2 gene. Methods: WES performed on DNA sample. Population and bioinformatics analysis were performed. Result: The NM_ 001099274.3(TINF2): c.844C>T (p.Arg282Cys) mutation was found by WES. Conclusion: There was no history of the disease in the family, and the variant was classified as a de novo mutation. 
Type of Study: Case Report | Subject: Medical Biotechnology

1. Niewisch MR, Savage SA. An update on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert review of hematology 2019; 12(12): 1037-1052. [DOI:10.1080/17474086.2019.1662720]
2. Agarwal S. Evaluation and management of hematopoietic failure in dyskeratosis congenita. Hematology/oncology clinics of north America 2018; 32(4): 669-685. [DOI:10.1016/j.hoc.2018.04.003]
3. Nishio N, Kojima S. Recent progress in dyskeratosis congenita. International journal of hematology 2010; 92(3): 419-424. [DOI:10.1007/s12185-010-0695-5]
4. Giri N, Ravichandran S, Wang Y, Gadalla SM, Alter BP, Fontana J, Savage SA. Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder. ERJ open research 2019; 5(4): 00209-2019. [DOI:10.1183/23120541.00209-2019]
5. Khincha PP, Dagnall CL, Hicks B, Jones K, Aviv A, Kimura M, Katki H, Aubert G, Giri N, Alter BP, Savage SA, Gadalla SM. Correlation of leukocyte telomere length measurement methods in patients with dyskeratosis congenita and in their unaffected relatives. International journal of molecular sciences 2017; 18(8): 1765. [DOI:10.3390/ijms18081765]
6. Kuznetsova V, Grozeva S, Gokhman V. Telomere structure in insects: A review. Journal of Zoological Systematics and Evolutionary Research 2019; 58(1): 127-158. [DOI:10.1111/jzs.12332]
7. De Leon AD, Cronkhite JT, Katzenstein ALA, Godwin JD, Raghu G, Glazer CS, Rosenblatt RL, Griod CE, Garrity ER, Xing C, Garcia CK. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PloS one 2010; 5(5):e10680. [DOI:10.1371/journal.pone.0010680]
8. Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. American journal of human genetics 2008; 82(2): 501-509. [DOI:10.1016/j.ajhg.2007.10.004]
9. Cicconi A, Chang S. Shelterin and the replisome: at the intersection of telomere repair and replication. Current opinion in genetics and development 2020; 60: 77-84. [DOI:10.1016/j.gde.2020.02.016]
10. Sarper N, Zengin E, Kılıç SÇ. A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex. Pediatric blood and cancer 2010; 55(6): 1185-1186. [DOI:10.1002/pbc.22624]
11. Yang D, He Q, Kim H, Ma W, Songyang Z. TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase. Journal of biological chemistry 2011; 286(26): 23022-23030. [DOI:10.1074/jbc.M111.225870]
12. Frescas D, de Lange T. A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice. Genes and development 2014; 28(2): 153-166. [DOI:10.1101/gad.233395.113]
13. Knight SW, Heiss NS, Vulliamy TJ, Greschner S, Stavrides G, Pai GS, Lestringant G, Varma N, Mason PJ, Dokal I, Poustka A. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. The American journal of human genetics 1999; 65(1): 50-58. [DOI:10.1086/302446]
14. Nelson ND, Dodson LM, Escudero L, Sukumar AT, Williams CL, Mihalek I, Baldan A, Baired DM, Bertuch AA. The C-terminal extension unique to the long isoform of the shelterin component TIN2 enhances its interaction with TRF2 in a phosphorylation-and dyskeratosis congenita cluster-dependent fashion. Molecular and cellular biology 2018; 38(12): e00018-e00025. [DOI:10.1128/MCB.00025-18]
15. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 2008; 112(9): 3594-3600. [DOI:10.1182/blood-2008-05-153445]
16. Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proceedings of the national academy of sciences of the united states of America 2005; 102(44): 15960-15964. [DOI:10.1073/pnas.0508124102]
17. Canudas S, Smith S. Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells. Journal of cell biology 2009; 187(2): 165-173. [DOI:10.1083/jcb.200903096]
18. Kim Sh, Beausejour C, Davalos AR, Kaminker P, Heo SJ, Campisi J. TIN2 mediates functions of TRF2 at human telomeres. Journal of biological chemistry 2004; 279(42): 43799-43804. [DOI:10.1074/jbc.M408650200]
19. Sasa GS, Ribes‐ Zamora A, Nelson ND, Bertuch AA. Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood. Clinical genetics 2012; 81(5): 470-478. [DOI:10.1111/j.1399-0004.2011.01658.x]
20. XIN ZT, Ly H. Characterization of interactions between naturally mutated forms of the TIN2 protein and its known protein partners of the shelterin complex. Clinical genetics 2012; 81(3): 301-302. [DOI:10.1111/j.1399-0004.2011.01784.x]
21. Hu C, Rai R, Huang C, Broton C, Long J, Xu Y, Xue J, Lei M, Chang S, Chen Y. Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex. Cell research 2017; 27(12): 1485-1502. [DOI:10.1038/cr.2017.144]
22. Ghilain C, Gilson E, Giraud-Panis MJ. Multifunctionality of the telomere-capping shelterin complex explained by variations in its protein composition. Cells 2021; 10(7):1753. [DOI:10.3390/cells10071753]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2023 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb