Send to

Choose Destination
Blood Cells Mol Dis. 2008 Mar-Apr;40(2):185-191. doi: 10.1016/j.bcmd.2007.08.002. Epub 2007 Oct 23.

Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes.

Author information

Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Department of Hematology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan.
Contributed equally


As the incidence of bone-marrow failure syndromes (BMFS) is 2-3x higher in East Asia than in the West, we examined peripheral blood or marrow cells of 100 Japanese patients for possible pathogenic mutations in the two main components of the telomere-synthesizing enzyme telomerase (hTERC RNA and hTERT protein) that have recently been implicated in the disease pathogenesis. We analyzed samples collected from 34 patients with acquired aplastic anemia (AA), 66 patients with myelodysplastic syndromes (MDS) and 120 healthy controls. In addition to two polymorphic germ-line sequence changes (n-771A/G and n-714 C insertion) in the promoter region of hTERC and eleven hTERT polymorphisms that were identified in both patients and healthy individuals, we found a novel germ-line C323T mutation in the hTERC RNA in an MDS patient only. This heterozygous C323T mutation abolished telomerase enzymatic activity and functioned in a haploinsufficiency manner to modulate telomerase activity in cells. In summary, this study reports a novel telomerase natural variant that abolishes telomerase function, which may lead to telomere shortening and marrow hypocellularity in patients with BMFS. This study also highlights the rarity of genetic alterations in BMFS patients in Japan, which suggests that other factors may play a more prominent role in the disease pathogenesis in East Asia.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center