Isolated Gonadotropin-Releasing Hormone Deficiency (IGD) is a condition characteristically marked by the absence or delay of puberty. Previous work suggests that there is a disconnect between the hypothalamus and pituitary in the hypothalamic-pituitary gonadal (HPG) axis that may be a cause for this condition. In particular, the expression of Kisspeptin, as well as GnRH, in the hypothalamus are vital aspects of the HPG axis for maintaining fertility. Whole exome sequencing performed on IGD patients revealed mutations in a gene called ZIC1. There has been little to no previous work done on the role of ZIC1 in the reproductive system. We developed a patient mutation model in the immortalized KTaV and KTaR cell lines to test the implications of ZIC1 on the expression of Kisspeptin. We also use the GT1-7 cell line to test ZIC1 on expression of GnRH. In our study, we find that novel patient mutations in ZIC1 reverse ZIC1 effects on Kisspeptin luciferase and GnRH luciferase expression. Select mutations also produce truncated proteins and display a dispersion of localization in the cell. Our results provide preliminary mechanisms that support further study of the etiology of IGD as well as identifying a novel gene that regulates the HPG axis.