Clinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism

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dc.authoridAKBULUT, EKREM/0000-0002-7526-9835|camtosun, emine/0000-0002-8144-4409|dogan, mustafa/0000-0003-0464-6565|Dundar, Ismail/0000-0003-1468-6405;
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.accessioned2025-10-24T18:09:58Z
dc.date.available2025-10-24T18:09:58Z
dc.date.issued2023
dc.departmentMalatya Turgut Özal Üniversitesi
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.
dc.identifier.doi10.4274/jcrpe.galenos.2023.2022-10-14
dc.identifier.endpage171
dc.identifier.issn1308-5727
dc.identifier.issn1308-5735
dc.identifier.issue2
dc.identifier.pmid36700485
dc.identifier.startpage160
dc.identifier.trdizinid1177675
dc.identifier.urihttps://doi.org/10.4274/jcrpe.galenos.2023.2022-10-14
dc.identifier.urihttps://search.trdizin.gov.tr/tr/yayin/detay/1177675
dc.identifier.urihttps://hdl.handle.net/20.500.12899/3914
dc.identifier.volume15
dc.identifier.wosWOS:001001916000007
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakTR-Dizin
dc.language.isoen
dc.publisherGalenos Publ House
dc.relation.ispartofJournal Of Clinical Research In Pediatric Endocrinology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20251023
dc.subjectProtein modelling; hypogonadotropic hypogonadism; genetic analyses
dc.titleClinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism
dc.typeArticle

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