Male Infertility via the CATSPER1 Gene

Male infertility is a reproductive disorder affecting 10-20% of couples worldwide. CATSPER1-related male infertility is a heritable form of nonsyndromic male infertility (NSMI). This condition results from abnormalities in sperm. Routine semen analysis from affected individuals typically identifies sperm defects and reduced fertility suggestive of asthenozoospermia. Men with CATSPER1-related NSMI showed normal pH, but nonmotile sperm or sperm motility below the normal threshold, low sperm count, increased abnormally structured spermatozoa, and reduced semen volume (Avenarius et al. 2009). Men with CATSPER1-related NSMI do not have any other symptoms.

CATSPER1-related nonsyndromic male infertility is inherited in an autosomal recessive manner. At least two loss-of-function variants in CATSPER1 have been identified to cause this condition. The CATSPER1 protein belongs to a CATSPER family of four sperm-specific voltage-gated calcium channels. CATSPER1 is expressed exclusively in the testis, and is localized primarily to the principal piece of the sperm tail (Ren et al. 2001). It was demonstrated that the CATSPER1 protein is required for Ca²⁺ entry into the sperm cell and Ca²⁺-mediated hyperactivated sperm motility (Ren et al. 2001; Carlson et al. 2003). The two known insertion variants in CATSPER1 were thought to result in the production of a severely truncated CATSPER1 protein that lacks all transmembrane domains and the channel pore. As a result, sperm cells missing the functional CATSPER1 protein were unable to penetrate the egg and achieve fertilization (Avenarius et al. 2009; Hildebrand et al. 2010).

CATSPER1 pathogenic variants have only been identified in two unrelated families with male infertility (Avenarius et al. 2009).

To date, no large deletions or duplications have been reported involving CATSPER1 (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the CATSPER1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).