First evidence of involvement of TBC1D25 in causing human male infertility

Eur J Med Genet. 2021 Feb;64(2):104142. doi: 10.1016/j.ejmg.2021.104142. Epub 2021 Jan 15.

Abstract

Male infertility is a heterogeneous disorder which may result from disruption in molecular and cellular pathways involved in spermatogenesis. Several reports have described abnormal spermatogenesis because of defective autophagy in model organisms. In the present study, we have clinically and genetically characterized a family segregating oligozoospermia in X-linked pattern. Exome sequencing revealed a disease-causing missense variant [NM_002536, c.149 A > C, p.(Glu50Ala)] in TBC1D25, an autophagy gene located on human chromosome Xp11.23. In view of broad expression of the gene in testes and effect of the variant on its interaction with ATG8 homologues, we consider a possible role for the TBC1D25 variant in causing oligozoospermia in the present family. This is the first report describing the involvement of TBC1D25 in causing male infertility.

Keywords: Infertility; Novel variant; Oligozoospermia; Protein interaction; TBC1D25.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Apoptosis Regulatory Proteins / metabolism
  • Binding Sites
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism
  • Humans
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Mutation, Missense
  • Oligospermia / genetics*
  • Oligospermia / pathology
  • Protein Binding
  • Testis / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • GABARAP protein, human
  • GTPase-Activating Proteins
  • Microtubule-Associated Proteins
  • TBC1D25 protein, human