Seyedeh Zahra Mousavi
1 
, Pegah Kouhi
2, Vahid Esmaeili
3, Zeynab Rokhsattalab
2, Abdolreza Esmaeilzadeh
4, Navid Almadani
2, Bahram Mohammad Soltani
* , Mehdi Totonchi
2* 1 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
3 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
4 Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran
Abstract
Introduction: Unexplained male infertility (UMI) refers to a situation where no underlying cause of male infertility is defined during investigations of the couple.
Methods: Whole exome sequencing (WES) was performed to identify variants associated with UMI in a consanguineous Iranian family.
Results: 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.
Conclusion: 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.