Background: GnRH neurons originate outside the CNS in the olfactory placode and migrate into the central nervous system, becoming integral components of the hypothalamic-pituitarygonadal axis (HPG).
Objective and hypotheses: We hypothesize that gene(s), whose products are important for pubertal development can be identified via autozygosity mapping together with whole exome sequencing in patients with idiopathic hypogonadotrophic hypogonadism (IHH)/Kallmann Syndrome (KS).
Method: We studied a cohort IHH/KS cases.
Results: Our studies revealed three independent families in which IHH/KS is associated with inactivating CCDC141 variants.
Conclusion: These results indicate that CCDC141 is required for successful migration of GnRH neurons to their final destination in the hypothalamus, and thus establishment of the central part of HPG axis.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology