Prohibited Olympic Medalist with PIEZO1 VUS Who Claims Innocence

Competitive athletes are often exposed to extreme physiological loading, resulting in over excessive mechanotransduction during their acute intensive training sessions and competitions. Individual differences in their genetics often affect how they cope with these challenges, as reflected in their high performances. Olympic Medalists are prohibited from providing atypical values in the Hematological Module of the Athlete Biological Passport. Since there was no aphysiological result and the Athlete maintained his innocence, a whole genome sequence analysis was carried out on him and his parents, with the primary focus on the <i>PIEZO</i> ion channels encoding gene. <i>PIEZO1</i> is known to participate in homeostatic regulation even on a whole-body level, including the regulation of physical performance, circulatory longevity of red blood cells and cell fate determination of mesenchymal stem cells in relation to hydrostatic pressure. However, <i>PIEZO2</i> was found to be the principal mechanosensory ion channel for proprioception. These regulatory mechanisms play a pivotal role in mechanotransduction and intensive exercise moments. Interestingly, two variances of uncertain significance of <i>PIEZO1</i> were found that may explain the atypical values of the Athlete. Furthermore, two additional variances in <i>SDC2</i>, the syndcan-2 encoding gene, were identified in trans position that may influence the crosstalk between <i>PIEZO2</i> and <i>PIEZO1</i>, with more likely relevance to the detected atypical values. After all, based on the found variances of <i>PIEZO1</i> and syndecan-2, it cannot be ruled out that these VUS variants may have caused or impacted the exhibited outlier findings of the ABP Hematological Module of the Athlete.