A homozygous PIWIL1 frameshift variant triggers azoospermia and reveals a strong selective constraint on germline genome integrity

Taken as a whole, these data reinforce the body of evidence showing that PIWIL1 is essential for human spermatogenesis and highlight the importance of the piRNA pathway in safeguarding the male germline. Defects in genome defence mechanisms might therefore constitute an underexplored cause of human male infertility.