J Clin Res Pediatr Endocrinol. 2017; 9(2): 95-100 | DOI: 10.4274/jcrpe.3908

Hypogonadotropic Hypogonadism due to Novel FGFR1 Mutations

Gamze Akkuþ¹, Leman Damla Kotan², Erdem Durmaz³, Eda Mengen², Ýhsan Turan², Ayça Ulubay⁴, Fatih Gürbüz², Bilgin Yüksel², Tamer Tetiker¹, A. Kemal Topaloðlu^2
1Çukurova University Faculty Of Medicine, Division Of Endocrinology, Adana, Turkey
²Çukurova 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.

Keywords: Hypogonadotropic hypogonadism, FGFR1 mutations, Kallmann syndrome, reduced penetrance

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