CAPS Mutations Are Potentially Associated with Unexplained Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL) is a major concern for women's reproductive health. Several studies have proved that genetics is a major factor leading to unexplained RPL, but the maternal pathogenic genes involved in RPL remain largely unknown. A consanguineousfamily, including the parents who were cousinsand their three daughters who had been diagnosed as having nonsyndromic unexplained RPL, was recruited in this study. A rare homozygous variant in calcyphosine ( CAPS ; ENST00000588776: c.377delC, p.Leu127Trpfs) might be the potential candidate variant for this RPL family through whole- exome sequencing. Sanger sequencingconfirmed that the three affected sisters carried the homozygous p.Leu127Trpfs, whereas their parents carried the heterozygous p.Leu127Trpfs. CAPS encodes a Ca 2+ -binding protein and may play a role in the regulation of Ca 2+ transport. Although the precise underlying mechanisms remain unclear, the previous study suggested that they may be involved in cross talk between Ca 2+ signaling and cAMP–protein kinase A pathways, which are crucial to embryo implantation and pregnancy maintenance. Knockdown of CAPS expression might promote the expression of secreted phosphoprotein1 and matrix metalloproteinase 9, and the release of prostaglandin E 2 , which all played important roles in embryo implantation and early pregnancy maintenance. These results indicated that the autosomal recessive homozygous mutation, p.Leu127Trpfs, in CAPS might be a maternal effectcausative mutation of RPL pathogenesis.