Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita

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Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita

Dyskeratosis congenita (DC) is a premature ageing syndrome characterised by short telomeres. An X-linked form of DC is caused by mutations in DKC1 which encodes dyskerin, a telomerase component that is essential for telomerase RNA stability. However, mutations in DKC1 are identifiable in only half of X-linked DC families. A four generation family with pulmonary fibrosis and features of DC was i...

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Skewed X-inactivation in carriers of X-linked dyskeratosis congenita.

A gene causing Dyskeratosis Congenita (DC), a rare genetic disorder associated with bone marrow failure, has been mapped to chromosome Xq28, but autosomal inheritance of the disease has also been reported. We have investigated the pattern of X-inactivation in the peripheral blood of carriers of DC using the methylation-sensitive Hpa II site in the androgen receptor gene (HUMARA). In 5 different...

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Missense mutation in a patient with X-linked dyskeratosis congenita.

We report the case of a 40-year-old male patient with dyskeratosis congenita(DKC). Sequencing of the DKC1 gene revealed an inherited missense mutation in base 1050 (GC), changing methionine to isoleucine. This is the third description of a mutation in codon 350 (exon 11), changing a very well conserved amino acid in the pseudouridine synthase (PUA) domain of dyskerin.

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A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells.

Dyskerin gene is mutated in patients with X-linked dyskeratosis congenita (X-DC), which results in greatly reduced levels of telomerase activity. A genetic suppressor element (GSE) termed GSE24-2 has been isolated in a screening for cisplatin resistance. GSE24-2-expressing cells presented impaired telomerase inhibition following in vitro exposure to chemotherapies, such as cisplatin, or telomer...

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Enhanced telomere shortening in transformed lymphoblasts from patients with X linked dyskeratosis.

AIM Dyskeratosis congenita (DC) is characterised by the failure of those tissues that are rapidly dividing in the adult, particularly the skin, mucosae, and haemopoietic system. The X linked form of the disease is caused by mutations of the DKC1 gene, which encodes dyskerin, a protein that is necessary for the function of telomerase. Cultured DC lymphoblastoid cells are characterised by a reduc...

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ژورنال

عنوان ژورنال: Journal of Medical Genetics

سال: 2011

ISSN: 0022-2593,1468-6244

DOI: 10.1136/jmg.2010.085100