Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes

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Kırkgöz T., GÜRSOY S., Acar S., Nalbantoğlu Ö., Özkaya B., Korkmaz H. A., ...Daha Fazla

Archives of Endocrinology and Metabolism, cilt.68, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 68
  • Basım Tarihi: 2023
  • Doi Numarası: 10.20945/2359-4292-2022-0254
  • Dergi Adı: Archives of Endocrinology and Metabolism
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: combined pituitary hormone deficiency, GLI2, isolated growth hormone deficiency, LHX4, Pituitary, Hypopituitarism, POU1F1, PROP1
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.