A de novo TINF2, R282C Mutation in a Case of Dyskeratosis Congenital Founded by Next-Generation Sequencing

Background: 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 was performed on DNA sample of the proband, and the variant was investigated in the family by Sanger sequencing. Population and bioinformatics analysis were performed. Results: 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.

[1]  E. Gilson,et al.  Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition , 2021, Cells.

[2]  Sandy Chang,et al.  Shelterin and the replisome: at the intersection of telomere repair and replication. , 2020, Current opinion in genetics & development.

[3]  V. Gokhman,et al.  Telomere structure in insects: A review , 2020 .

[4]  S. Savage,et al.  An update on the biology and management of dyskeratosis congenita and related telomere biology disorders , 2019, Expert review of hematology.

[5]  S. Savage,et al.  Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder , 2019, ERJ Open Research.

[6]  Suneet Agarwal.  Evaluation and Management of Hematopoietic Failure in Dyskeratosis Congenita. , 2018, Hematology/oncology clinics of North America.

[7]  I. Mihalek,et al.  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 , 2018, Molecular and Cellular Biology.

[8]  Yong Chen,et al.  Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex , 2017, Cell Research.

[9]  A. Aviv,et al.  Correlation of Leukocyte Telomere Length Measurement Methods in Patients with Dyskeratosis Congenita and in Their Unaffected Relatives , 2017, International journal of molecular sciences.

[10]  David Frescas,et al.  A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice , 2014, Genes & development.

[11]  A. Bertuch,et al.  Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood , 2012, Clinical genetics.

[12]  Z. Xin,et al.  Characterization of interactions between naturally mutated forms of the TIN2 protein and its known protein partners of the shelterin complex , 2012, Clinical genetics.

[13]  Z. Songyang,et al.  TIN2 Protein Dyskeratosis Congenita Missense Mutants Are Defective in Association with Telomerase* , 2011, The Journal of Biological Chemistry.

[14]  N. Sarper,et al.  A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex , 2010, Pediatric blood & cancer.

[15]  S. Kojima,et al.  Recent progress in dyskeratosis congenita , 2010, International journal of hematology.

[16]  G. Raghu,et al.  Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations , 2010, PloS one.

[17]  Susan Smith,et al.  Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells , 2009, The Journal of cell biology.

[18]  T. Vulliamy,et al.  TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes , 2008, Blood.

[19]  N. Orr,et al.  TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. , 2008, American journal of human genetics.

[20]  Yen-Pei Christy Chang,et al.  Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Campisi,et al.  TIN2 Mediates Functions of TRF2 at Human Telomeres* , 2004, Journal of Biological Chemistry.

[22]  A. Poustka,et al.  X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. , 1999, American journal of human genetics.