Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1.
| Autor: | Kotan LD, Cooper C, Darcan Ş, Carr IM, Özen S, Yan Y, Hamedani MK, Gürbüz F, Mengen E, Turan İ, Ulubay A, Akkuş G, Yüksel B, Topaloğlu AK; Çukurova University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Adana, Turkey Phone: +90 322 338 60 60-3148 E-mail: ktopaloglu@cu.edu.tr., Leygue E |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Journal of clinical research in pediatric endocrinology [J Clin Res Pediatr Endocrinol] 2016 Jun 05; Vol. 8 (2), pp. 125-34. Date of Electronic Publication: 2016 Apr 18. |
| DOI: | 10.4274/jcrpe.3248 |
| Abstrakt: | Objective: What initiates the pubertal process in humans and other mammals is still unknown. We hypothesized that gene(s) taking roles in triggering human puberty may be identified by studying a cohort of idiopathic hypogonadotropic hypogonadism (IHH). Methods: A cohort of IHH cases was studied based on autozygosity mapping coupled with whole exome sequencing. Results: Our studies revealed three independent families in which IHH/delayed puberty is associated with inactivating SRA1 variants. SRA1 was the first gene to be identified to function through its protein as well as noncoding functional ribonucleic acid products. These products act as co-regulators of nuclear receptors including sex steroid receptors as well as SF-1 and LRH-1, the master regulators of steroidogenesis. Functional studies with a mutant SRA1 construct showed a reduced co-activation of ligand-dependent activity of the estrogen receptor alpha, as assessed by luciferase reporter assay in HeLa cells. Conclusion: Our findings strongly suggest that SRA1 gene function is required for initiation of puberty in humans. Furthermore, SRA1 with its alternative products and functionality may provide a potential explanation for the versatility and complexity of the pubertal process. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|