DLG2 Mutations in the Etiology of Pubertal Delay and Idiopathic Hypogonadotropic Hypogonadism


TURAN İ., DEMİR K., Mengen E., KOTAN L. D., GÜRBÜZ F., YÜKSEL B., ...Daha Fazla

HORMONE RESEARCH IN PAEDIATRICS, cilt.94, sa.9-10, ss.364-368, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 94 Sayı: 9-10
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1159/000520409
  • Dergi Adı: HORMONE RESEARCH IN PAEDIATRICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, SportDiscus
  • Sayfa Sayıları: ss.364-368
  • Anahtar Kelimeler: Idiopathic hypogonadotropic hypogonadism, DLG2, Oligogenic inheritance, SEQUENCE VARIANTS, GENETICS
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Introduction: Idiopathic hypogonadotropic hypogonadism (IHH) is caused by dysfunction of the hypothalamic-pituitary-gonadal axis. DLG2 was recently implicated as a gene associated with delayed puberty and which may also contribute to IHH. The confirmation of the candidate puberty genes in independent IHH cohorts has become crucial due to the lack of proper genotype-phenotype segregations in reported pedigrees. Therefore, we aimed to screen DLG2 in patient variants in a large cohort of IHH patients. Methods: The present study included a total of 336 IHH patients from 290 independent families. The coding and flanking regions of DLG2 were screened for potentially important variants in the WES data. Candidate variants were evaluated in the -gnomAD and GME databases according to their allele frequencies, and only those with a frequency Results: We found 1 homozygous and 2 heterozygous missense variants in 3 independent pedigrees. Identified variants were found extremely rare or not reported in gnomAD. Two variants were categorized as "uncertain significance," and the other one was "likely pathogenic" according to the ACMG criteria. All patients were normosmic, and in 2 of the 3 families, there were no causal variants in other IHH-related genes. Conclusion: We detected 3 rare sequencing variants in DLG2 in 5 patients with IHH or delayed puberty in a large IHH cohort. Our results support the contention that the DLG2 mutations are associated with IHH in human puberty.