Sperm from a patient with a homozygous in-frame deletion in CATSPERE lack functional CatSper expression and fail to fertilise at IVF

Background: CatSper is a multi-subunit sperm-specific calcium channel that mediates the progesterone-induced increase in intracellular calcium. Evidence from CatSper subunit knock-out mouse models implicates it as essential for sperm fertilisation competence. Similarly, impaired or absent P4 response in patient sperm is associated with poor or loss of fertilisation at IVF. However, genetic evidence in a limited number of cases reported genomic deletions spanning a number of loci. We reported a unique case (Williams et al., 2014) of a man (patient 1) with sperm that lacked functional CatSper expression but he had no genetic errors in CatSper subunit coding regions. Subsequently, two new proteins have been proposed to be part of the mature complex (CatSper-epsilon and CatSper-zeta).