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Genetic profiles and three-year follow-up study of Chinese males with congenital hypogonadotropic hypogonadism
  • +5
  • Luyao Zhang,
  • Yuting Gao,
  • Qin Du,
  • Liyi Liu,
  • Yanbing Li,
  • Subrata Dey,
  • Santasree Banerjee,
  • Zhihong Liao
Luyao Zhang
Sun Yat-sen University First Affiliated Hospital
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Yuting Gao
Sun Yat-sen University First Affiliated Hospital
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Qin Du
Sun Yat-sen University First Affiliated Hospital
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Liyi Liu
Sun Yat-sen University First Affiliated Hospital
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Yanbing Li
Sun Yat-sen University First Affiliated Hospital
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Subrata Dey
Maulana Abul Kalam Azad University of Technology
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Santasree Banerjee
Jilin University
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Zhihong Liao
Sun Yat-sen University First Affiliated Hospital
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Abstract

Genotypes-phenotypes correlation and treatment outcomes for 73 Chinese CHH male patients was performed in this study. Patients self-selected one of the four treatments: pulsatile Gonadorelin® pump, cyclical gonadotropins therapy, human menopausal gonadotropin monotherapy, or testosterone replacement treatment. Clinical assessments were performed every 3 months for 3 years. Baseline clinical features, spermatogenesis and secondary sexual development outcomes were analyzed. Whole exome sequencing identified 63 variants in 52 patients (70%), 18 of which were novel. Variants on FGFR1, PROKR2, CHD7, ANOS1 and NSMF gene were 10 (15.87%), 10 (15.87%), 7(11.11%), 5(7.93%) and 5(7.93%) respectively. Some null variants could lead to severe clinical manifestations than missense variants on FGFR1 and CHD7. The Lasso regression model for spermatogenic failure risk showed that cryptorchidism history, abnormal epididymis or prostate, lower basal LH and peak-LH post Triptorelin® stimulation were significant predictors. Approximately, 30% normosmic patients defined by simple olfactory assessment showed olfactory nerve center maldevelopment with nasal sinus MRI. The severity of reproductive system was attributed to spermatogenesis that could be predicted by nomogram model. No direct correlation was observed between candidate genes and spermatogenic outcome, however, the clinical severity is partially related with specific variants, and clinical features might in turn affect the treatment efficacy.