Clinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism

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dc.authoridDundar, Ismail/0000-0003-1468-6405
dc.authoridÇamtosun, Emine/0000-0002-8144-4409
dc.authoriddogan, mustafa/0000-0003-0464-6565
dc.authoridAKBULUT, EKREM/0000-0002-7526-9835
dc.authorwosidDundar, Ismail/ABG-2027-2021
dc.authorwosidÇamtosun, Emine/AAE-3945-2020
dc.authorwosidÇiftci, Nurdan/GNM-8116-2022
dc.contributor.authorCiftci, Nurdan
dc.contributor.authorAkinci, Aysehan
dc.contributor.authorAkbulut, Ekrem
dc.contributor.authorCamtosun, Emine
dc.contributor.authorDundar, Ismail
dc.contributor.authorDogan, Mustafa
dc.contributor.authorKayas, Leman
dc.date.accessioned2024-08-04T20:10:20Z
dc.date.available2024-08-04T20:10:20Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractObjective: Idiopathic hypogonadotropic hypogonadism (IHH) is classified into two groups-Kalman syndrome and normosmic IHH (nIHH). Half of all cases can be explained by mutations in >50 genes. Targeted gene panel testing with nexrt generation sequencing (NGS) is required for patients without typical phenotypic findings. The aim was to determine the genetic etiologies of patients with IHH using NGS, including 54 IHH-associated genes, and to present protein homology modeling and protein stability analyzes of the detected variations.Methods: Clinical and demographic data of 16 patients (eight female), aged between 11.6-17.8 years, from different families were assessed. All patients were followed up for a diagnosis of nIHH, had normal cranial imaging, were without anterior pituitary hormone deficiency other than gonadotropins, had no sex chromosome anomaly, had no additional disease, and underwent genetic analysis with NGS between the years 2008-2021. Rare variants were classified according to the variant interpretation framework of the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology. Changes in protein structure caused by variations were modeled using RoseTTAFold and changes in protein stability resulting from variation were analyzed.Results: Half of the 16 had no detectable variation. Three (18.75%) had a homozygous (pathogenic) variant in the GNRHR gene, one (6.25%) had a compound heterozygous [likely pathogenic-variants of uncertain significance (VUS)] variant in PROK2 and four (25%) each had a heterozygous (VUS) variant in HESX1, FGF8, FLRT3 and DMXL2. Protein models showed that variants interpreted as VUS according to ACMG could account for the clinical IHH.Conclusion: The frequency of variation detection was similar to the literature. Modelling showed that the variant in five different genes, interpreted as VUS according to ACMG, could explain the clinical IHH.en_US
dc.identifier.doi10.4274/jcrpe.galenos.2023.2022-10-14
dc.identifier.endpage171en_US
dc.identifier.issn1308-5727
dc.identifier.issn1308-5735
dc.identifier.issue2en_US
dc.identifier.pmid36700485en_US
dc.identifier.scopus2-s2.0-85160873133en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage160en_US
dc.identifier.trdizinid1177675en_US
dc.identifier.urihttps://doi.org/10.4274/jcrpe.galenos.2023.2022-10-14
dc.identifier.urihttps://search.trdizin.gov.tr/yayin/detay/1177675
dc.identifier.urihttps://hdl.handle.net/11616/92720
dc.identifier.volume15en_US
dc.identifier.wosWOS:001001916000007en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakTR-Dizinen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherGalenos Publ Houseen_US
dc.relation.ispartofJournal 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.subjectProtein modellingen_US
dc.subjecthypogonadotropic hypogonadismen_US
dc.subjectgenetic analysesen_US
dc.titleClinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadismen_US
dc.typeArticleen_US

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