FaCD Online Syndrome Fact Sheet

Last updated: 25 Mar 2010

Name: TERT Mutation-Associated Haematological Disorders

Mode of Inheritance: AD

Genes

TERT, mapped to 5p15.33

Tumor features

leukemia, acute myeloblastic (AML, M2)
leukemia, chronic lymphocytic (CLL)
myelodysplastic syndrome (MDS)
non-Hodgkin lymphoma

Non-tumor features

anemia, aplastic
liver cirrhosis

Comment

Germline mutations in the telomere-specific reverse transcriptase (TERT) gene can cause a variety of disorders including congenital dyskeratosis, associated with a wide range of tumor types, and pulmonary fibrosis. However, mutations have also been observed in patients without these two disorders, who had been diagnosed with aplastic anemia[1], often with a family history of MDS, in patients with acute myeloid leukemia[2] and in patients with CLL or diffuse large B cell lymphoma[3]. Liver cirrhosis has been observed in these families[4]. Levels of penetrance of the TERT mutations are not yet clear.

See also Myelodysplasia and Acute Myeloid Leukemia (AML), Familial

References

[1] Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005 Apr 7;352(14):1413-24.
[2] Calado RT, Regal JA, Hills M, Yewdell WT, Dalmazzo LF, Zago MA, Lansdorp PM, Hogge D, Chanock SJ, Estey EH, Falcão RP, Young NS. Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1187-92.
[3] Hills M, Lansdorp PM. Short telomeres resulting from heritable mutations in the telomerase reverse transcriptase gene predispose for a variety of malignancies. Ann N Y Acad Sci. 2009 Sep;1176:178-90.
[4] Calado RT, Regal JA, Kleiner DE, Schrump DS, Peterson NR, Pons V, Chanock SJ, Lansdorp PM, Young NS. A spectrum of severe familial liver disorders associate with telomerase mutations.PLoS One. 2009 Nov 20;4(11):e7926.