-Review-

Mutations of Telomerase Complex Genes Linked to Bone Marrow Failures

Hiroki Yamaguchi

Department of Pathophysiological Management/Medical Oncology, Graduate School of Medicine, Nippon Medical School

Dyskeratosis congenita (DKC) is a bone marrow failure (BMF) with characteristic physical anomalies, and is typically diagnosed in childhood. Some forms of DKC are known to be caused by mutations occurring in DKC1, telomerase RNA component (TERC), and telomerase reverse transcriptase (TERT). These genes are the main constituents of the telomerase complex that plays a role in replicating telomeres and stabilizing them against shortening. Mutations in these genes could shorten telomeres and impair the proliferative capacity of hematopoietic stem cells, eventually causing DKC. Recently, mutations in TERC and TERT have been reported in some cases of aplastic anemia (AA) and myelodysplastic syndrome (MDS). These cases are considered to be atypical forms of DKC that develop slowly in adulthood without characteristic physical anomalies. Genetic tests are essential in diagnosing this late-presenting DKC and determining the appropriate treatment. This article reviews mutations in the telomerase complex and their connections with DKC and bone marrow failures.

J Nippon Med Sch 2007; 74: 202-209

Keywords
bone marrow failure, dyskeratosis congenita, telomere, telomerase complex gene, mutation

Correspondence to
Hiroki Yamaguchi, MD, Ph D, Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
y-hiroki@fd6.so-net.ne.jp

Received, November 30, 2006
Accepted, December 29, 2006