IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2010;4(3):187-192

Original Article
Functional characterization of mutations in the promoter proximal region of the
telomerase hTERC gene identified in patients with hematological disorders

Kathryn A. Carroll, Hinh Ly

Emory University School of Medicine, Pathology and Laboratory Medicine Department, Atlanta, GA, USA.

Received June 15, 2011; accepted July 25, 2011; Epub September 15, 2011; published September 30, 2011

Abstract: Telomerase RNA gene (hTERC) mutations have been identified in a subset of patients with bone-marrow failure syndromes
(BMFS).  While most of the mutations were found in the coding region of hTERC, some rare disease-associated mutations as well as
polymorphic sequence changes were found in the promoter proximal region of the gene, including the -99C/G sequence change that
was implicated to modulate hTERC gene expression by disrupting Sp1 transcriptional factor binding.  We and other researchers
recently identified, in addition to the -99C/G mutation, several other sequence variations (-240delCT, -714+C insertion, and -771A/G) in
the hTERC promoter in other cohorts of patients with blood disorders.  Using a convenient telomerase reconstitution assay coupled
with the hTERC-promoter driven luciferase reporter assay, we characterized each of the hTERC’s promoter sequence variants and
found that these rare sequence changes did not negatively affect telomerase gene expression or function.  We therefore conclude that
all known mutations in the promoter proximal region of the hTERC gene do not necessarily contribute to the pathogenesis of
hematological disorders by directly affecting telomerase transcriptional activity and/or its enzymatic function.  (IJCEM1106003).

Key words: Telomeres, telomerase, bone-marrow failure syndromes, gene promoter analysis

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Address all correspondence to:
Dr. Hinh Ly
Emory University School of Medicine
615 Michael St., Whitehead Biomedical Research Building, room 105L
Atlanta, GA 30322, U.S.A.
Tel: (404) 712-2841
Fax: (404) 727-8538
E-mail: hly@emory.edu