ADAMTS13 gene; a novel splicing site mutation in a case with thrombotic thrombocytopenic purpura

Sepideh Zununi Vahed,Seyed Sadroddin Rasi Hashemi,Behzad Zaker,Alessandra Cremaschi,Mohammadreza Ardalan

doi:10.34172/npj.2021.17

Abstract

A plasma protease, ADAMTS13, cleaves the von Willebrand factor (VWF) and its deficiency is associated with the pathogenesis of thrombotic thrombocytopenic purpura (TTP). According to the Human Gene Mutation Database (HGMD), about 150 mutations have been identified in the ADAMTS13 gene. A 23-year-old man, with hematuria and gingival bleeding was admitted to our University Hospital. Four years ago he was diagnosed with a TTP history. During these years, he was under intermittent plasma exchange. A blood sample was taken for genetic study. He effectively responded to one session of fresh frozen plasma replacement and plasma exchange. Genetic study indicated that this case carries two heterozygous mutations in ADAMTS13 gene; a novel splicing variant (c.2610+5G>A) and a nonsense p.Arg910X mutation that previously is reported to relate to TTP. The novel variant predicted to result in an aberrant ADAMTS13 transcript processing.

Highlights

Thrombotic thrombocytopenic purpura (TTP) is identified by small-vessel platelet-rich thrombi and presents with microangiopathic hemolytic anemia, thrombocytopenia, and consequent multiorgan dysfunction [1]
Implication for health policy/practice/research/medical education: The c.2728C>T (p.Arg910X) mutation in ADAMTS13 gene was found in a patient with congenital TTP
Deficiency of a plasma protease ADAMTS13 cleaving the von Willebrand factor (VWF), can result in VWF perseverance that plays an important role in the pathogenesis of TTP [2]

Summary

Introduction

Thrombotic thrombocytopenic purpura (TTP) is identified by small-vessel platelet-rich thrombi and presents with microangiopathic hemolytic anemia, thrombocytopenia, and consequent multiorgan dysfunction [1]. Implication for health policy/practice/research/medical education: The c.2728C>T (p.Arg910X) mutation in ADAMTS13 gene was found in a patient with congenital TTP. We found c.2610+5G>A mutation, a novel splicing variant, that affects exon 20 and encodes for the ADAMTS13’s thrombospondin type-1 fifth domain in this case. This novel variant expected to cause aberrant ADAMTS13 transcript processing.

Results

Conclusion