• PMID: 19344877
• Gene Name: CatSper1
• Condition: Male infertility
• Association: Associated
• Mutation: CATSPER1 (c.539-540insT, c.948-949insATGGC, p.Lys180LysfsX8, p.Asp317MetfsX18)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: CATSPER1
• Other associated phenotypes: Male infertility

Human male infertility caused by mutations in the CATSPER1 channel protein

Avenarius MR, Hildebrand MS, Zhang Y, Meyer NC, Smith LL, Kahrizi K, Najmabadi H, Smith RJ.

Male infertility, a common barrier that prevents successful conception, is a reproductive difficulty affecting 15% of couples. Heritable forms of nonsyndromic male infertility can arise from single-gene defects as well as chromosomal abnormalities. Although no CATSPER gene has been identified as causative for human male infertility, male mice deficient for members of the CatSper gene family are infertile. In this study, we used routine semen analysis to identify two consanguineous Iranian families segregating autosomal-recessive male infertility. Autozygosity by descent was demonstrated in both families for a approximately 11 cM region on chromosome 11q13.1, flanked by markers D11S1765 and D11S4139. This region contains the human CATSPER1 gene. Denaturing high-performance liquid chromatography (DHPLC) and bidirectional sequence analysis of CATSPER1 in affected family members revealed two separate insertion mutations (c.539-540insT and c.948-949insATGGC) that are predicted to lead to frameshifts and premature stop codons (p.Lys180LysfsX8 and p.Asp317MetfsX18). CATSPER1 is one of four members of the sperm-specific CATSPER voltage-gated calcium channel family known to be essential for normal male fertility in mice. These results suggest that CATSPER1 is also essential for normal male fertility in humans. FAU - Avenarius, Matthew R AU - Avenarius MR AD - Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI 48109-0618, USA. FAU - Hildebrand, Michael S AU - Hildebrand MS FAU - Zhang, Yuzhou AU - Zhang Y FAU - Meyer, Nicole C AU - Meyer NC FAU - Smith, Luke L H AU - Smith LL FAU - Kahrizi, Kimia AU - Kahrizi K FAU - Najmabadi, Hossein AU - Najmabadi H