Idiopathic hypogonadotropic hypogonadism caused by inactivating mutations in SRA1

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dc.contributor.authorKotan L.D.
dc.contributor.authorCooper C.
dc.contributor.authorDarcan Ş.
dc.contributor.authorCarr I.M.
dc.contributor.authorÖzen S.
dc.contributor.authorYan Y.
dc.contributor.authorHamedani M.K.
dc.contributor.authorGürbüz F.
dc.contributor.authorMengen E.
dc.contributor.authorTuran İ.
dc.contributor.authorUlubay A.
dc.contributor.authorAkkuş G.
dc.contributor.authorYüksel B.
dc.contributor.authorTopaloğlu A.K.
dc.contributor.authorLeygue E.
dc.date.accessioned2019-10-27T08:20:35Z
dc.date.available2019-10-27T08:20:35Z
dc.date.issued2016
dc.departmentEge Üniversitesien_US
dc.description.abstractObjective: 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. © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.en_US
dc.description.sponsorshipMedical Research Council, MRC: MR/L01629X/1en_US
dc.identifier.doi10.4274/jcrpe.3248en_US
dc.identifier.endpage134en_US
dc.identifier.issn1308-5727
dc.identifier.issue2en_US
dc.identifier.pmid27086651en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage125en_US
dc.identifier.urihttps://doi.org/10.4274/jcrpe.3248
dc.identifier.urihttps://hdl.handle.net/11454/25717
dc.identifier.volume8en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherGalenos Yayincilik,en_US
dc.relation.ispartofJCRPE Journal of Clinical Research in Pediatric Endocrinologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectHypogonadotropic hypogonadismen_US
dc.subjectMutationen_US
dc.subjectPNPLA6en_US
dc.subjectPubertyen_US
dc.subjectSRA1en_US
dc.titleIdiopathic hypogonadotropic hypogonadism caused by inactivating mutations in SRA1en_US
dc.typeArticleen_US

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