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Dyskeratosis Congenita
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The CTC1/STN1/TEN1 (CST) complex promotes extension of the C-rich strand of telomere DNA after telomerase has elongated the G-rich strand of the telomere DNA, creating extension of the duplex telomere DNA component.
Ophthalmic findings and a novel CTC1 gene mutation in coats plus syndrome: a case report
Published in Ophthalmic Genetics, 2021
Tingyi Liang, Xiang Zhang, Yu Xu, Peiquan Zhao
The molecular pathogenesis of Coats plus syndrome was unclear until 2012. CTC1 gene mutation was confirmed to be the causative gene of Coats plus syndrome by Anderson et al. from 10 families with Coats plus syndrome (1). Meanwhile, shortened telomeres were observed in patients with Coats plus syndrome. CTC1 gene, located on chromosome 17p13.1, encodes CTC1 protein, which is a component of the CTC1-STN1-TEN1 (CST) complex (7,8). CST complex binds to single-stranded DNA (ssDNA) in a high affinity and sequence-independent manner, and associates with a fraction of telomeres, which may participate in DNA metabolism and telomere protection (9). Individuals with CTC1 gene mutations display shortened telomeres and telomere dysfunction, which result in disease pathogenesis (3). We identified a compound heterozygous mutation (c.2954_2956del, p.C985del and c.33 + 1 G > T) in CTC1 gene, which may cause Coats plus syndrome in our present patient. Mutation c.2954_2956del (p.C985del) is a deletion mutation and results in a reduction of amino acids in CTC1 protein, which has been reported by Anderson (1). The c.33 + 1 G > T mutation is a novel splicing site mutation, which leads to abnormal splicing of CTC1 pre-RNA, resulting in an impaired CTC1 protein.
An update on the biology and management of dyskeratosis congenita and related telomere biology disorders
Published in Expert Review of Hematology, 2019
Marena R. Niewisch, Sharon A. Savage
In addition to shelterin and the telomerase complex, the CST complex (CTC1, STN1, and TEN1) and other proteins (RTEL1, TCAB1, PARN), which directly or indirectly interact with any of the before mentioned proteins, play essential roles in telomere maintenance (see Figure 2 and Table 1). The CST complex is involved in telomere capping, interacts with shelterin proteins, and can also modulate telomerase access to the telomere [48]. RTEL1 is a DNA helicase with various functions in the telomeric context such as t-loop unwinding, duplex telomeric DNA replication and prevention of catastrophic telomere loss during cell division [49]. In interaction with TPP1 and TERT, TCAB1 functions in the recruitment of the assembled telomerase at the Cajal bodies and its trafficking to the telomere [50]. PARN is a deadenylase that processes mRNAs and non-coding RNA, including TERC [51–53].
Unilateral Coats’-like disease and an intragenic deletion in the TERC gene: A case report
Published in Ophthalmic Genetics, 2018
G. Peene, E. Smets, E. Legius, C. Cassiman
The exact molecular mechanism underlying Coats’ disease is unknown, but Coats plus syndrome, also known as CRMCC, is an autosomal recessive disorder. Coats plus syndrome joined the spectrum of DC with the discovery that it is caused by mutations in a telomere-capping gene. Coats plus is caused by mutations in the telomere protein conserved telomere maintenance component1 (CTC1) or STN1. Members of the CTC1-STN1-TEN1 (CST) complex are critical for telomere replication. Several patients with Coats plus display critically shortened telomeres, suggesting that telomere dysfunction plays an important role in disease pathogenesis (8). The discovery that bone marrow failure and telomere dysfunction are present in patients with Coats plus syndrome provides yet another compelling link between disruption of telomere homeostasis and ocular pathology (14).