Activation of a cryptic splice site in a potentially lethal coagulation defect accounts for a functional protein variant.

ABSTRACT: Changes at the invariable donor splice site +1 guanine, relatively frequent in human genetic disease, are predicted to abrogate correct splicing, and thus are classified as null mutations. However, their ability to direct residual expression, which might have pathophysiological implications in several diseases, has been poorly investigated. As a model to address this issue, we studied the IVS6+1G>T mutation found in patients with severe deficiency of the protease triggering coagulation, factor VII (FVII), whose absence is considered lethal. In expression studies, the IVS6+1G>T induced exon 6 skipping and frame-shift, and prevented synthesis of correct FVII transcripts detectable by radioactive/fluorescent labelling or real-time RT-PCR. Intriguingly, the mutation induced the activation of a

SUBMITTER: Cavallari N 

PROVIDER: S-EPMC3787739 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature