|
|
Blood, 15 August 2007, Vol. 110, No. 4, pp. 1141-1146.
Prepublished online as a Blood First Edition Paper on May 3, 2007; DOI 10.1182/blood-2007-03-080044.
 Previous Article | Next Article 
Submitted March 14, 2007
Accepted April 29, 2007
Mutations in the SBDS gene in acquired aplastic anemia
Rodrigo T. Calado*, Solomon A. Graf, Keisha L. Wilkerson, Sachiko Kajigaya, Philip J. Ancliff, Yigal Dror, Stephen J. Chanock, Peter M Lansdorp, and Neal S. Young
Hematology Branch, NHLBI/NIH, Bethesda, MD, United States
Howard Hughes Medical Institute, NIH Research Scholars Program, Bethesda, MD, United States
Camelia Botnar Laboratories, Great Ormond Street Hospital, London, United Kingdom
Cell Biology Program, Research Institute, Hospital For Sick Children and the University of Toronto, Toronto, ON, Canada
Pediatric Oncology Branch, NCI/NIH, Gaithersburg, MD, United States
Terry Fox Laboratory, BC Cancer Research Centre and the Department of Medicine, University of British Columbia, Vancouver, BC, Canada
* Corresponding author; email: calador{at}nhlbi.nih.gov.
Shwachman-Diamond syndrome (SDS; OMIM 260400), an inherited bone marrow failure syndrome, is caused by mutations in both alleles of the SBDS gene, which encodes a protein of unknown function. Here we report heterozygosity for the 258+2 T C SBDS gene mutation previously identified in SDS patients in 4 of 91 patients with apparently acquired aplastic anemia (AA) but not in 276 ethnically-matched controls (Fisher's exact test, P=.0037). Affected patients were young and had a poor outcome; they had reduced SBDS expression but no evidence of the pancreatic exocrine failure or skeletal abnormalities typical of SDS. Length of telomeres in granulocytes of SBDS heterozygous patients was short for their age, and in SDS patients with both SBDS alleles affected further analyzed, granulocytes' telomeres were even shorter, correlating in length with SBDS expression. Higher heterogeneity in telomere length also was observed in SDS patients. Telomerase activity of SBDS-deficient patients' lymphocytes was comparable to controls, and no physical interaction between SBDS protein and telomerase complex components (TERT or TERC) was established. We propose that heterozygosity for the 258+2 TC SBDS mutation predisposes to AA by accelerating telomere shortening of leukocytes via a telomerase-independent mechanism.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Yamaguchi, J. Takeuchi, H. Tamai, Y. Mitamura, F. Kosaka, K. Dan, and K. Inokuchi
Identification of the SBDS Gene Mutation in Japanese Patients with Bone Marrow Failure Syndrome
Blood (ASH Annual Meeting Abstracts),
November 16, 2008;
112(11):
4117 - 4117.
[Abstract]
|
|
|
|
|
|
|
R. T. Calado and N. S. Young
Telomere maintenance and human bone marrow failure
Blood,
May 1, 2008;
111(9):
4446 - 4455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. K. Garcia, W. E. Wright, and J. W. Shay
Human diseases of telomerase dysfunction: insights into tissue aging
Nucleic Acids Res.,
December 3, 2007;
35(22):
7406 - 7416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Wang, H. Yagasaki, A. Hama, N. Nishio, Y. Takahashi, and S. Kojima
Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children
Haematologica,
November 1, 2007;
92(11):
1573 - 1573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
