A homozygous telomerase T-motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal Hreidarsson syndrome.

ABSTRACT: Hoyeraal Hreidarsson syndrome (HHS) is a form of dyskeratosis congenita (DC) characterized by bone marrow failure, intrauterine growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency, and extremely short telomeres. As with DC, mutations in genes encoding factors required for telomere maintenance, such as telomerase reverse transcriptase (TERT), have been found in patients with HHS. We describe 2 sibling HHS cases caused by a homozygous mutation (p.T567M) within the TERT T motif. This mutation resulted in a marked reduction in the capacity of telomerase to processively synthesize telomeric repeats, indicating a role for the T motif in this unique aspect of telomerase function. We support this finding by demonstrating defective processivity in the prev

SUBMITTER: Gramatges MM 

PROVIDER: S-EPMC3643759 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature