Poly(A)-specific ribonuclease deficiency in patients with dyskeratosis congenita скачать в хорошем качестве

Poly(A)-specific ribonuclease deficiency in patients with dyskeratosis congenita

The inherited disorder dyskeratosis congenita is characterized by short telomeres, mucocutaneous abnormalities, and bone marrow failure. The underlying genetic mutations are known in approximately 40% of cases and are found within genes associated with telomere maintenance and function. In this episode, Tom Vulliamy and Hemanth Tummala discuss their work, which identifies biallelic mutations in the gene encoding poly(A)-specific ribonuclease (PARN) in 3 families with severe dyskeratosis congenita. These mutations inhibit the deadenylation activity of PARN, resulting in the downregulation of 4 genes involved in telomere maintenance and shortened telomeres. The results of this study establish a causative role for PARN in a severe form of dyskeratosis congenita.