The Action will investigate the neuroendocrine mechanisms that are integrated at the hypothalamic level and regulate the complex organ network controlling reproduction. Implicated genes/pathways have been identified through genetic investigations of rare patients with isolated GnRH deficiency, who display reproductive failure. Despite knowledge of 16 disease genes, multiple additional genes/mechanisms remain undiscovered, requiring higher-order collaborations for full elucidation. Through a collaborative network of physician-scientists and biologists, the Action will deliver: (i) a database with de-identified genetic and phenotypic data on at least 1,000 GnRH-deficient patients, their families, and unaffected controls; (ii) 1 or more disease gene(s) in each patient, and/or 10 or more novel disease genes; (iii) elucidation of newly identified genes’ roles in animal/cell-based systems; and (iv) guidelines for genetic counseling of GnRH-deficient patients based on the emerging disease architecture. Reasons for undertaking the Action in the COST framework are: (i) a critical yet disjointed mass of experts exists across Europe; (ii) participants are currently nationally funded; (iii) several participants’ countries do not participate in the e-RARE2 European funding scheme for rare diseases. European leadership in reproductive research/medicine will be augmented by the Action’s anticipated benefits; (i) collaboration among previously competing groups; (ii) shared use of cutting-edge genetic methodologies; and (iii) recruitment/training of young investigators.
GnRH deficiency - Kallmann syndrome - genetics - reproduction - translational research
