Whole-Exome Sequencing Analysis of Idiopathic Hypogonadotropic Hypogonadism: Comparison of Varicocele and Nonobstructive Azoospermia.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 101291249 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1933-7205 (Electronic) Linking ISSN: 19337191 NLM ISO Abbreviation: Reprod Sci Subsets: MEDLINE
    • Publication Information:
      Publication: 2020- : [New York] : Springer
      Original Publication: Thousand Oaks, Calif. : Sage
    • Subject Terms:
      Azoospermia*/genetics ; Varicocele*/genetics ; Hypogonadism*/genetics ; Hypogonadism*/diagnosis; Adult ; Humans ; Male ; Exome Sequencing ; Mutation
    • Abstract:
      As a rare disease leading to male infertility, idiopathic hypogonadotropic hypogonadism (IHH) has strong heterogeneity of clinical phenotype and gene mutation. At present, there is no effective diagnosis and treatment method for this disease. This study is to explore the possible new pathogenic gene of idiopathic hypogonadotrophic hypogonadism and the pathological mechanism affecting its occurrence. We performed a whole-exome sequencing on 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), 19 varicocele patients with asthenospermia, oligospermia, or azoospermia, 5 patients with simple nonobstructive azoospermia, and 13 normal healthy adult males and carried out comparative analysis, channel analysis, etc. After preliminary sequencing screening, 309-431 genes harbouring variants, including SNPs and indels, were predicted to be harmful per single patient in each group. In genetic variations of nIHH patients' analysis, variants were detected in 10 loci and nine genes in nine patients. And in co-analysis of the three patient groups, nine nIHH patients, 19 VC patients, and five SN patients shared 116 variants, with 28 variant-harbouring genes detected in five or more patients. We found that the NEFH, CCDC177, and PCLO genes and the Gene Ontology pathways GO:0051301: cell division and GO:0090066: regulation of anatomical structure size may be key factors in the pathogenic mechanism of IHH. Our results suggest that the pathogenic mechanism of IHH is not limited to the central nervous system effects of GnRH but may involve other heterogeneous pathogenic genetic variants that affect peripheral organs.
      (© 2023. The Author(s).)
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    • Grant Information:
      2022NSFSC1281 Natural Science Foundation of Sichuan Province; 2022NSFSC1508 Science and technology department of sichuan university; Q20055 Sichuan Federation of Social Science Associations
    • Contributed Indexing:
      Keywords: Normosmic idiopathic hypogonadotropic hypogonadism; Varicocele; Whole exon sequence; nIHH
    • Subject Terms:
      Idiopathic Hypogonadotropic Hypogonadism; Azoospermia, Nonobstructive
    • Publication Date:
      Date Created: 20230907 Date Completed: 20240115 Latest Revision: 20240925
    • Publication Date:
      20240925
    • Accession Number:
      PMC10784340
    • Accession Number:
      10.1007/s43032-023-01337-2
    • Accession Number:
      37679557