Pathogenic homozygous PLCZ1 mutation reduces sperm protein levels with a simulated reduction of PIP2 binding: a case report

In this study, we examined two unrelated men who had been unable to have children despite multiple IVF (in vitro fertilisation) attempts. We discovered that both men carried the same mutation in a gene called PLCZ1. This gene normally produces a protein in sperm that tells the egg to begin developing into an embryo, but because of the mutation in these men, the sperm could not deliver that message to the egg. Interestingly, this same mutation had previously only been reported in Chinese patients, and this was the first time it was found in men from a different ethnic background, suggesting that this mutation may be a globally occurring mutation. This finding could help doctors recognise similar fertility problems in other patients and could lead to more effective treatments in the future.