ESPE Abstracts (2016) 86 FC12.3

Inactivating Mutations in CCDC141 Causing Idiopathic Hypogonadotrophic Hypogonadism/Kallmann Syndrome

Ihsan Turana, B. Ian Hutchinsb, Bulent Hacıhamdiogluc, Mehmet Nuri Ozbekd, Leman Damla Kotana, Yusuf Ozkane, Hudson Stonerb, Paul J. Chengb, Fatih Gurbuza, Eda Mengena, Bilgin Yuksela, Susan Wrayb & Kemal Topaloglua

aCukurova University, Division of Pediatric Endocrinology, Adana, Turkey; bCellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, USA; cDepartment of Pediatric Endocrinology, GATA Medical Faculty, Istanbul, Turkey; dDepartment of Pediatric Endocrinology, Diyarbakir Children’s State Hospital, Diyarbakir, Turkey; eDepartment of Endocrinology, Firat University, Elazig, Turkey

Background: GnRH neurons originate outside the CNS in the olfactory placode and migrate into the central nervous system, becoming integral components of the hypothalamic-pituitary–gonadal 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.