A male patient harboring the mutations R331X and X399R demonstrated (1) increased sensitivity to exogenous pulsatile GnRH compared to a cohort of I</span>HH patients undergoing similar therapy and (2) steady increases in testicular volume, spermatogenesis, and fertility while on long-term GnRH therapy.
The patient carrying the compound heterozygous mutations (R331X and X399R) had attenuated secretion of endogenous gonadotropin-releasing hormone and a left-shifted dose-response curve for gonadotropin-releasing hormone as compared with six patients who had idiopathic hypogonadotropic hypogonadism without GPR54 mutations.