|
|
Blood, 1 February 2008, Vol. 111, No. 3, pp. 1128-1130.
Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-10-120907.
 Previous Article | Table of Contents | Next Article 
CLINICAL TRIALS AND OBSERVATIONS
Brief Report
Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene
Hong-Yan Du1,
Elena Pumbo1,
Peter Manley2,
Joshua J. Field1,
Susan J. Bayliss1,3,
David B. Wilson3,
Philip J. Mason1, and
Monica Bessler1
1 Department of Internal Medicine, Washington University School of Medicine, St Louis, MO;
2 Department of Pediatric Hematology and Oncology, Brown University School of Medicine, Providence, RI; and
3 Department of Pediatrics, Washington University School of Medicine, St Louis, MO
Heterozygous mutations in the telomerase components TERT, the reverse transcriptase, and TERC, the RNA template, cause autosomal dominant dyskeratosis congenita due to telomere shortening. Anticipation, whereby the disease severity increases in succeeding generations due to inheritance of shorter telomeres, is a feature of this condition. Here we describe 2 families in which 2 TERT mutations are segregating. Both families contain compound heterozygotes. In one case the proband is homozygous for a novel mutation causing a P704S substitution, while his father's second allele encodes an H412Y mutation. The proband in the second family has mutant alleles Y846C and H876Q. Transfection studies show codominant expression of the mutated alleles with no evidence of a dominant negative effect or of intragenic complementation. Thus in these families the expression of both TERT alleles and the inherited telomere length contribute to the clinical phenotype.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. T. Calado, J. A. Regal, M. Hills, W. T. Yewdell, L. F. Dalmazzo, M. A. Zago, P. M. Lansdorp, D. Hogge, S. J. Chanock, E. H. Estey, et al.
Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia
PNAS,
January 27, 2009;
106(4):
1187 - 1192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Du, E. Pumbo, J. Ivanovich, P. An, R. T. Maziarz, U. M. Reiss, D. Chirnomas, A. Shimamura, A. Vlachos, J. M. Lipton, et al.
TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements
Blood,
January 8, 2009;
113(2):
309 - 316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Walne, T. Vulliamy, R. Beswick, M. Kirwan, and I. Dokal
TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes
Blood,
November 1, 2008;
112(9):
3594 - 3600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. Alder, J. J.-L. Chen, L. Lancaster, S. Danoff, S.-c. Su, J. D. Cogan, I. Vulto, M. Xie, X. Qi, R. M. Tuder, et al.
Short telomeres are a risk factor for idiopathic pulmonary fibrosis
PNAS,
September 2, 2008;
105(35):
13051 - 13056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Vulliamy, R. Beswick, M. Kirwan, A. Marrone, M. Digweed, A. Walne, and I. Dokal
From the Cover: Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita
PNAS,
June 10, 2008;
105(23):
8073 - 8078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
