Telomeres,p53, Hepatocyte Nuclear Factor 4α, and Liver Disease.

Abstract

Dyskeratosis congenita is an inherited disorder characterized by defects in the ability of cells to maintain telomeres. Patients commonly present with pediatric bone marrow failure and liver and/or pulmonary fibrosis in the fourth to fifth decade of life. The prevalence of dyskeratosis congenita is estimated as 1 in 1 million; however, due to the incomplete penetrance of disease, the true prevalence is unknown.[1] Defects in at least 10 distinct telomere-associated genes lead to the development of premature stem cell and tissue failure. Patients with dyskeratosis congenita also have a predisposition to develop cancer; approximately 5% develop hepatocellular carcinoma.[2] Interestingly, in the general population, hepatocellular carcinoma often arises in the setting of cirrhosis and shortened hepatic telomeres and is associated with reactivation of hepatic telomerase in more than 90% of patients.