ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume: 16 Issue: 1 Year: 2024
Forms

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1 [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2016; 8(2): 125-134 | DOI: 10.4274/jcrpe.3248

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

Leman Damla Kotan1, Charlton Cooper2, Şükran Darcan3, Ian M. Carr4, Samim Özen3, Yi Yan2, Mohammad K. Hamedani2, Fatih Gürbüz1, Eda Mengen1, İhsan Turan1, Ayça Ulubay5, Gamze Akkuş6, Bilgin Yüksel1, A. Kemal Topaloğlu1, Etienne Leygue2
1Çukurova University Faculty Of Medicine, Department Of Pediatrics, Division Of Pediatric Endocrinology, Adana, Turkey
2University Of Manitoba, Manitoba Institute Of Cell Biology, Winnipeg, Manitoba, Canada
3Ege University Faculty Of Medicine, Department Of Pediatrics, Division Of Pediatric Endocrinology, İzmir, Turkey
4University Of Leeds, Institute Of Biomedical And Clinical Sciences, Section Of Genetics, Leeds, United Kingdom
5Çukurova University Faculty Of Medicine, Department Of Forensic Medicine, Adana, Turkey
6Çukurova University Faculty Of Medicine, Division Of Endocrinology And Metabolism, Adana, Turkey

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.

Keywords: Hypogonadotropic hypogonadism,puberty,SRA1,PNPLA6,mutation

Leman Damla Kotan, Charlton Cooper, Şükran Darcan, Ian M. Carr, Samim Özen, Yi Yan, Mohammad K. Hamedani, Fatih Gürbüz, Eda Mengen, İhsan Turan, Ayça Ulubay, Gamze Akkuş, Bilgin Yüksel, A. Kemal Topaloğlu, Etienne Leygue. Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1. J Clin Res Pediatr Endocrinol. 2016; 8(2): 125-134
Manuscript Language: English
LookUs & Online Makale