Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes.
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.
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA.
Shahinaz M
SM
Gadalla
Richard
R
Cawthon
Neelam
N
Giri
Blanche P
BP
Alter
Sharon A
SA
Savage
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic; D029503:Anemia, Diamond-Blackfan / Q000235:genetics; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D002610:Cheek; D002648:Child; D019871:Dyskeratosis Congenita / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000166:cytology*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult