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 PIEZO ion channels encoding gene. PIEZO1 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, PIEZO2 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 PIEZO1 were found that may
explain the atypical values of the Athlete. Furthermore, two additional variances
in SDC2, the syndcan-2 encoding gene, were identified in trans position that may influence
the crosstalk between PIEZO2 and PIEZO1, with more likely relevance to the detected
atypical values. After all, based on the found variances of PIEZO1 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.