Homozygous nonsense mutation Trp28X in the LHB gene causes male hypogonadism

J Assist Reprod Genet. 2018 May;35(5):913-919. doi: 10.1007/s10815-018-1133-5. Epub 2018 Feb 23.

Abstract

Purpose: The purpose of this study was to investigate a novel mutation in the luteinizing hormone beta-subunit (LHB) gene in one male patient with hypogonadism due to selective luteinizing hormone (LH) deficiency.

Methods: Sanger sequencing of one 28-year-old man born to consanguineous parents was performed. Treatment with human chorionic gonadotropin (hCG) (2000 IU, twice a week) was initiated for 3 months, followed by 5000 IU weekly to date.

Results: We identified a novel c.84G>A[p.W28X] nonsense LHB mutation. The W28X mutation produces a truncated LHB peptide of seven amino acids, which prevents the synthesis of intact LH. After 40 days of treatment with hCG, the patient exhibited a few spermatozoa in the semen. Treated for 6 months, the patient exhibited normal seminal parameters.

Conclusions: We identified a novel mutation in the LHB gene in a male patient with hypogonadism and provided evidence that LHB nonsense mutation can cause selective LH deficiency. We reconfirmed hCG treatment may restore male fertility due to LHB mutation.

Keywords: Luteinizing hormone; Luteinizing hormone beta subunit; Primary hypogonadotropic hypogonadism; Selective luteinizing hormone deficiency.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chorionic Gonadotropin / therapeutic use
  • Codon, Nonsense*
  • Female
  • Homozygote
  • Humans
  • Hypogonadism / drug therapy
  • Hypogonadism / genetics*
  • Luteinizing Hormone / deficiency*
  • Luteinizing Hormone / genetics
  • Luteinizing Hormone, beta Subunit / genetics*
  • Male
  • Pedigree

Substances

  • Chorionic Gonadotropin
  • Codon, Nonsense
  • Luteinizing Hormone, beta Subunit
  • Luteinizing Hormone