# Duplication of the prothrombin gene is associated with a significant increase in thrombin generation

## TL;DR

A woman with a duplication in her prothrombin gene had increased blood clotting risk, a new finding in thrombosis research.

## Contribution

This is the first reported case of a full prothrombin gene duplication linked to hypercoagulability.

## Key findings

- The duplication encompassed the entire prothrombin gene and six adjacent protein-coding genes.
- The duplication was associated with markedly increased prothrombin levels and thrombin generation.
- The patient had a history of unprovoked arterial and venous thrombotic episodes.

## Abstract

Prothrombin gene mutations can be associated with either a thrombotic or a bleeding risk. Genomic studies and coagulation workup can provide valuable information to better understand their clinical importance.

We describe the case of a woman with a duplication of the entire prothrombin gene.

A 42-year-old woman presented for thrombophilia screening following a history of unprovoked arterial and superficial venous thrombotic episodes. Coagulation workup demonstrated a marked increase in prothrombin levels and ex vivo thrombin generation. Genetic analysis revealed a duplication of at least 307.9 kb (maximum 366.7 kb): arr[ChRCh38]:11p11.2(46,455,533-46,763,446)x3, encompassing the entire prothrombin gene and 6 adjacent protein-coding genes (HARBI1, ATG13, ARHGAP1, and ZNF408 completely involved, and AMBRA1 and CKAP5 partially involved).

The present case demonstrated duplication of the entire prothrombin gene, associated with a significant hypercoagulable risk, a finding not previously reported in the literature.

•A prothrombin gene duplication was detected in a woman with a history of unprovoked thromboses.•Gene analysis revealed a duplication of at least 307.9 kb (maximum 366.7 kb).•This duplication encompassed the entire prothrombin gene and 6 adjacent protein-coding genes.•The mutation was associated with markedly increased prothrombin levels and thrombin generation.

A prothrombin gene duplication was detected in a woman with a history of unprovoked thromboses.

Gene analysis revealed a duplication of at least 307.9 kb (maximum 366.7 kb).

This duplication encompassed the entire prothrombin gene and 6 adjacent protein-coding genes.

The mutation was associated with markedly increased prothrombin levels and thrombin generation.