Identifying a CATSPERB Variants in unexplained male infertility through familial exome sequencing

Unexplained male infertility (UMI) refers to a situation where no underlying cause of male infertility is defined during investigations of the couple.

Whole exome sequencing (WES) was performed to identify variants associated with UMI in a consanguineous Iranian family.

WES revealed a rare homozygous missense variant (chr14:g.92088086C>T; NM_024764.4:c.2126G>A; p.Arg709Gln) located in the extracellular region of CATSPERB in three affected siblings. This mutation resulted in the substitution of arginine 709 (R) with glutamine (Q) and co-segregated with the phenotype in other available family members. The kinematic parameters of sperm motility indicated abnormal hyperactivated movement. In-silico protein stability analysis suggests that the Arg709Gln (R709Q) alteration reduces the stability of the CATSPERB protein, potentially compromising causing defects in the overall stability of the CatSper complex.

Our findings provide initial evidence supporting the involvement of CATSPERB variants in UMI. This is the first reported genetic variant within the CATSPERB gene associated with UMI.