Scholarlink

Background <p>Male infertility (MI) is a polygenic condition mainly induced by spermatogenic failure/arrest or systemic disease with a large clinical spectrum. Lately, genetic sequencing allowed the identification of several variants implicated in both aforesaid situations.</p> Methods and results <p>In this case study, we performed whole exome sequencing (WES) on the genomic DNA of a 37-year-old Moroccan man with Non-Obstructive Azoospermia. Results revealed two variants in genes highly expressed in testicular tissue. The first was a heterozygous frameshift variant in the <i>AURKC</i> gene, causing a premature stop codon at position 71 of the AURKC protein, critical for spermatogenesis. The second was a hemizygous missense variant in the <i>ABCD1</i> gene, resulting in an H299R substitution in the ABCD1 protein, essential for transporting Very Long Chain Fatty Acids (VLCFAs) into peroxisomes. <i>ABCD1</i> variants are linked to X-linked Adrenoleukodystrophy (X-ALD), a disease caused by VLCFAs accumulation in cells. The patient’s family pedigree suggests X-linked transmission of MI, which may be a subclinical form of late-onset X-ALD in affected members, indicating that the <i>ABCD1</i> variant likely affects spermatogenesis. This hypothesis is supported by literature linking X-ALD to MI, <i>ABCD1</i>’s high expression in human testes, and the significant impact of the H299R substitution on ABCD1 transporter’s molecular dynamics.</p> Conclusions <p>These insights highlight the role of genetic mutations in male infertility, demonstrating that spermatogenesis can be disrupted either directly by specific mutations or indirectly through broader genetic disorders, underscoring the importance of comprehensive genetic testing.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Whole exome sequencing reveals ABCD1 variant as a potential contributor to male infertility

  • 期刊论文

  • 发表日期：

    2025年1月22日

查看全文
  • Salaheddine Redouane,
  • Houda Harmak,
  • Adil El Hamouchi,
  • Hicham Charoute,
  • Noureddine Louanjli,
  • Abderrahim Malki,
  • Abdelhamid Barakat,
  • Hassan Rouba

摘要

Background

Male infertility (MI) is a polygenic condition mainly induced by spermatogenic failure/arrest or systemic disease with a large clinical spectrum. Lately, genetic sequencing allowed the identification of several variants implicated in both aforesaid situations.

Methods and results

In this case study, we performed whole exome sequencing (WES) on the genomic DNA of a 37-year-old Moroccan man with Non-Obstructive Azoospermia. Results revealed two variants in genes highly expressed in testicular tissue. The first was a heterozygous frameshift variant in the AURKC gene, causing a premature stop codon at position 71 of the AURKC protein, critical for spermatogenesis. The second was a hemizygous missense variant in the ABCD1 gene, resulting in an H299R substitution in the ABCD1 protein, essential for transporting Very Long Chain Fatty Acids (VLCFAs) into peroxisomes. ABCD1 variants are linked to X-linked Adrenoleukodystrophy (X-ALD), a disease caused by VLCFAs accumulation in cells. The patient’s family pedigree suggests X-linked transmission of MI, which may be a subclinical form of late-onset X-ALD in affected members, indicating that the ABCD1 variant likely affects spermatogenesis. This hypothesis is supported by literature linking X-ALD to MI, ABCD1’s high expression in human testes, and the significant impact of the H299R substitution on ABCD1 transporter’s molecular dynamics.

Conclusions

These insights highlight the role of genetic mutations in male infertility, demonstrating that spermatogenesis can be disrupted either directly by specific mutations or indirectly through broader genetic disorders, underscoring the importance of comprehensive genetic testing.