Abstract

The ADAMTS13 gene plays an integral role in vascular homeostasis. A severe deficiency in ADAMTS13 triggers a rare disorder known as thrombotic thrombocytopenic purpura (TTP). Various missense and nonsense point mutations have been described in exonic regions of ADAMTS13 along with several frameshift deletions and one frameshift insertion. Additionally, several intronic mutations have been discovered in USA patients that result in aberrant mRNA splicing forms. A tissue based screen of ADAMTS13 alternative splicing has never been assessed. Besides the known mRNA splice isoforms, others are evident from the Expressed Sequence Tag (EST) databases. We analyzed alternative splicing of ADAMTS13 in several tissues in order to assess whether alternative splicing might play a role during its gene expression. We identified a novel isoform of ADAMTS13 that retains intron 25, evident in human, but not in mouse, hepatic cells. Moreover, the retained intron is not detected in mice possibly because they do not possess regulatory sites inserted into the human intron at a later evolutionary stage. This might suggest that ADAMTS13 is post-transcriptionally regulated at the splicing level. It also shows the need for future analysis of transcript levels of this new isoform in TTP patients. We hypothesize that irregular balance between the two splice isoforms might affect ADAMTS13 functionality, thus, it is possible that our findings might be of clinical significance.

“The findings and conclusions in this presentation have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.”

Disclosures: No relevant conflicts of interest to declare.

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