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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pathogenic TERT promoter variants in telomere diseases

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Gutierrez-Rodrigues, Fernanda [1, 2] ; Donaires, Flavia S. [2] ; Pinto, Andre [2] ; Vicente, Alana [1] ; Dillon, Laura W. [1] ; Cle, Diego V. [2] ; Santana, Barbara A. [2] ; Pirooznia, Mehdi [1] ; Ibanez, Maria del Pilar F. [1] ; Townsley, Danielle M. [1] ; Kajigaya, Sachiko [1] ; Hourigan, Christopher S. [1] ; Cooper, James N. [1] ; Calado, Rodrigo T. [2] ; Young, Neal S. [1]
Total Authors: 15
[1] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 - USA
[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Ribeirao Preto, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Genetics in Medicine; v. 21, n. 7, p. 1594-1602, JUL 2019.
Web of Science Citations: 5

Purpose: The acquisition of pathogenic variants in the TERT promoter (TERTp) region is a mechanism of tumorigenesis. In nonmalignant diseases, TERTp variants have been reported only in patients with idiopathic pulmonary fibrosis (IPF) due to germline variants in telomere biology genes. Methods: We screened patients with a broad spectrum of telomeropathies (n = 136), their relatives (n = 52), and controls (n = 195) for TERTp variants using a customized massively parallel amplicon-based sequencing assay. Results: Pathogenic -124 and -146 TERTp variants were identified in nine (7%) unrelated patients diagnosed with IPF (28%) or moderate aplastic anemia (4.6%); five of them also presented cirrhosis. Five (10%) relatives were also found with these variants, all harboring a pathogenic germline variant in telomere biology genes. TERTp clone selection did not associate with peripheral blood counts, telomere length, and response to danazol treatment. However, it was specific for patients with telomeropathies, more frequently co-occurring with TERT germline variants and associated with aging. Conclusion: We extend the spectrum of nonmalignant diseases associated with pathogenic TERTp variants to marrow failure and liver disease due to inherited telomerase deficiency. Specificity of pathogenic TERTp variants for telomerase dysfunction may help to assess the pathogenicity of unclear constitutional variants in the telomere diseases. (AU)

FAPESP's process: 15/19074-0 - Study of genetic factors associated with immunosuppression therapy in acquired aplastic anemia by whole exome sequencing
Grantee:Fernanda Gutierrez Rodrigues
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 14/27294-7 - Identification of genetic factors of response to immunosuppression in acquired aplastic anemia by next generation sequencing
Grantee:Fernanda Gutierrez Rodrigues
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC