Abstract
Telomeres, the nucleotide repeats and protein complex at chromosome ends, are required for chromosomal stability and are important markers of aging. Patients with dyskeratosis congenita (DC), an inherited bone marrow failure syndrome (IBMFS), have mutations in telomere biology genes, and very short telomeres. There are limited data on intra-individual telomere length (TL) variability in DC and related disorders. We measured relative TL by quantitative-PCR in blood, buccal cells, and fibroblasts from 21 patients with an IBMFS (5 Diamond-Blackfan anemia, 6 DC, 6 Fanconi anemia, and 4 Shwachman-Diamond syndrome). As expected, TL in patients with DC was significantly (p<0.01) shorter in all tissues compared with other IBMFS. In all disorders combined, the median Q-PCR TL was longer in fibroblast and buccal cells than in blood (overall T/S ratio=1.42 and 1.16 vs. 1.05, p=0.001, 0.006, respectively). Although the absolute values varied, statistically significant intra-individual correlations in TL were present in IBMFS patients: blood and fibroblast (r=0.66, p=0.002), blood and buccal cells (r=0.74, p<0.0001), and fibroblast and buccal cells (r=0.65, p=0.004). These data suggest that relative TL is tissue-independent in DC and possibly in the other IBMFS.
Highlights
Telomeres consist of long (TTAGGG)n nucleotide repeats and an ordered protein complex at the ends of chromosomes that are essential to maintaining chromosomal integrity [1]
Telomeres were significantly shorter in patients with dyskeratosis congenita (DC) than in patients with other inherited bone marrow failure syndrome (IBMFS) in blood, buccal cells (0.80 vs. 1.25, p=0.009), and fibroblasts (0.84 vs. 1.56, p=0.001) (Figure 1)
In all IBMFS patients combined, median Telomere length (TL) was longer in fibroblasts and buccal cells when compared with blood (1.42 and 1.16 vs. 1.05, p=0.001, 0.006, respectively) (Figure1)
Summary
Telomeres consist of long (TTAGGG)n nucleotide repeats and an ordered protein complex at the ends of chromosomes that are essential to maintaining chromosomal integrity [1]. Individuals with dyskeratosis congenita (DC), a cancer susceptibility and inherited bone marrow failure syndrome (IBMFS), have mutations in genes important in telomere biology, including DKC1, TERC, TERT, TINF2, NHP2 and NOP10 [4]. They have very short telomeres for age compared with unaffected family members or age-matched controls [5]. In order to better understand intra-individual TL variation in IBMFS, we compared TL, measured by QPCR, in DNA extracted from blood, buccal cells, and cultured fibroblasts within and between the four major IBMFS disorders, DC, FA, SDS, and DBA.
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