A novel frameshift mutation in ubiquitin-specific protease 26 gene in a patient with severe oligozoospermia

Abstract

Ubiquitin-specific protease 26 (USP26) encodes a predicted protein containing his- and cys- domains that are conserved among deubiquitinating enzymes. USP26 is specifically expressed in testis tissue and is a potential infertility gene. In the present study, we performed genetic testing related to spermatogenesis impairment in a patient with idiopathic severe oligozoospermia to identify the cause. The patient underwent clinical examination and reproductive hormone testing. Genes associated with male infertility, including USP26, were assessed by targeted exome sequencing. A novel frameshift mutation, c.2195delT (p.Phe732Serfs*14), was identified in USP26. This frameshift mutation was located in residue 732 of USP26 gene, leading to loss of the conserved deubiquitinating enzyme His-domain and producing a truncated protein of 744 amino acids. Bioinformatics analysis revealed this mutation to be pathogenic. A novel framshift mutation c.2195delT (p.Phe732Serfs*14) in USP26 gene was reported to be associated with male infertility in a Chinese patient with severe oligozoospermia.

The association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility: a systematic review and meta-analysis

“… 36 Nevertheless, the function of USP26 might be different between humans and mice. A frameshift mutation in the USP26 gene in a patient is reported to result in severe oligozoospermia, 37 which indicates a crucial role of USP26 in humans.…”

The function of nuclear hormone receptor 4A signaling in the human reproductive system: A review

“…Male factor infertility, as a common etiology of infertility, identified in up to 50% of infertile couples, as the sole contributing etiological factor or coupled with female factor infertility. 74,75 In addition to their increasingly well-studied roles in the context of female reproduction, nuclear hormone receptors serve as key regulators of spermatogenesis and associated hormone secretion. In this section, the importance of NR4A family proteins as regulators of spermatogenesis and hormone synthesis are discussed, as are the substances that can modulate NR4A receptor function to influence reproduction-related outcomes.…”

“…Male factor infertility, as a common etiology of infertility, identified in up to 50% of infertile couples, as the sole contributing etiological factor or coupled with female factor infertility 74,75 . In addition to their increasingly well‐studied roles in the context of female reproduction, nuclear hormone receptors serve as key regulators of spermatogenesis and associated hormone secretion.…”

Identification of novel homozygous missense and deletion mutations manifesting oligospermia infertility in Kashmiri population

“…7 Testicular variables associated with decreased sperm production include hereditary factors, radiation exposure and hormonal imbalance. 8,9 Varicocele is a clinical finding in oligospermia men, and it is present only in 10% of fertile men. Proposed mechanisms for damage to semen parameters such as sperm count and shape include a rise in scrotal temperature, reactive oxygen species generation, germ cell apoptosis and sperm DNA damage.…”