SUN-445 A NOVEL SPLICING SITE MUTATION IN ADAMTS13 GENE IN A PATIENT WITH THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

Abstract

Deficiency of ADAMTS13, a plasma protease that cleaves the von Willebrand factor (VWF) multimers, results in the persistence of high-molecular-weight multimers of VWF and has a major role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). A 23-year-old man with a clinical history of TTP since 4 years ago was admitted to our University Hospital because of gingival bleeding and hematuria. He was under intermittent plasma exchange during the last four years. He received last treatment for one month. A blood sample for the genetic study was taken. He successfully responds to one session of plasma exchange and FFP replacement. A genetic study found that the patient is carrying two heterozygous mutations in ADAMTS13 gene: a nonsense mutation (p.Arg910X) already associated with TTP and a novel splicing variant (c.2610+5G>A) predicted to cause aberrant processing of ADAMTS13 transcript. Mutations on these sequences can disrupt existing splice sites or splicing regulatory sequences (splicing silencers and enhancers), create new splicing sites, or activate the cryptic splicing sites that may lead to an aberrant transcript of the mutated gene. To estimate the possible effect of the identified changes, bioinformatic tools can be applied. However, it should be noted that the exact effect of the specific mutation should be verified with functional studies.