Hypogonadotropic Hypogonadism due to Novel FGFR1 Mutations
Gamze Akkuş1, Leman Damla Kotan2, Erdem Durmaz3, Eda Mengen2, İhsan Turan2, Ayça Ulubay4, Fatih Gürbüz2, Bilgin Yüksel2, Tamer Tetiker1, A. Kemal Topaloğlu21Çukurova University Faculty Of Medicine, Division Of Endocrinology, Adana, Turkey2Çukurova University Faculty Of Medicine, Division Of Pediatric Endocrinology, Adana, Turkey
3Izmir University Faculty Of Medicine, Division Of Pediatric Endocrinology, Izmir, Turkey
4Çukurova University Faculty Of Medicine, Department Of Forensic Medicine, Adana, Turkey
Objective: The underlying genetic etiology of hypogonadotropic hypogonadism (HH) is heterogeneous. Fibroblast growth factor signaling is pivotal in the ontogeny of gonadotropin-releasing hormone neurons. Loss-of-function mutations in FGFR1 gene cause variable HH phenotypes encompassing pubertal delay to idiopathic HH (IHH) or Kallmann syndrome (KS). As FGFR1 mutations are common, recognizing mutations and associated phenotypes may enhance clinical management.
Methods: Using a candidate gene approach, we screened 52 IHH/KS patients.
Results: We identified three novel (IVS3-1G>C and p.W2X, p.R209C) FGFR1 gene mutations. Despite predictive null protein function, patients from the novel mutation families had normosmic IHH without non-reproductive phenotype.
Conclusion: These findings further emphasize the great variability of FGFR1 mutation phenotypes in IHH/KS.
Manuscript Language: English
