The GnRHR gene, its mutations, and their phenotypic effects

The gonadotropin-releasing hormone (GnRH) receptor is an evolutionarily widespread central part of the GnRH network. As a member of the so-called G-protein-coupled receptor family, the transmembrane protein becomes activated by engagement due to binding of its ligand. The receptor is encoded byGnRHR, a gene mapping to human chromosome 4. Homozygous mutations found to be spread over all coding parts of exons ofGnRHRcan lead to idiopathic hypogonadotropic hypogonadism with stalled or even primarily absent onset of puberty. Founder effects have been described for some of these mutations and advantages for their heterozygous carriers due to an earlier occurrence of stress-induced amenorrhea are under discussion.