Abstract:
:Dyskeratosis congenita is a rare inherited disorder characterized by abnormal skin manifestations. Morbidity and mortality from this disease is usually due to bone marrow failure, but idiopathic pulmonary fibrosis and an increased cancer predisposition also occur. Families with autosomal dominant dyskeratosis congenita display anticipation and have mutations in the telomerase RNA gene. We identified a three-generation pedigree with autosomal dominant dyskeratosis congenita, anticipation, and telomere shortening. We show that a null mutation in motif D of the reverse transcriptase domain of the protein component of telomerase, hTERT, is associated with this phenotype. This mutation leads to haploinsufficiency of telomerase, and telomere shortening occurs despite the presence of telomerase. This finding emphasizes the importance of telomere maintenance and telomerase dosage for maintaining tissue proliferative capacity and has relevance for understanding mechanisms of age-related changes.
journal_name
Proc Natl Acad Sci U S Aauthors
Armanios M,Chen JL,Chang YP,Brodsky RA,Hawkins A,Griffin CA,Eshleman JR,Cohen AR,Chakravarti A,Hamosh A,Greider CWdoi
10.1073/pnas.0508124102keywords:
subject
Has Abstractpub_date
2005-11-01 00:00:00pages
15960-4issue
44eissn
0027-8424issn
1091-6490pii
0508124102journal_volume
102pub_type
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