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

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Abstract

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.

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Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

This research was supported through computational resources of HPC-MARWAN (hpc.marwan.ma) provided by the National Center for Scientific and Technical Research (CNRST), Rabat, Morocco.

Funding

No funds, grants, or other support was received.

Author information

Authors and Affiliations

  1. Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, Casablanca, Morocco

    Salaheddine Redouane, Houda Harmak, Abdelhamid Barakat & Hassan Rouba

  2. Genomic Sequencing Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco

    Salaheddine Redouane, Adil El Hamouchi, Hicham Charoute & Abdelhamid Barakat

  3. Laboratory of Physiopathology and Molecular Genetics, Department of Biology, Faculty of Sciences Ben M’Sick, Hassan II University, Casablanca, Morocco

    Salaheddine Redouane & Abderrahim Malki

  4. Research Unit of Epidemiology, Biostatistics and Bioinformatics, Institut Pasteur du Maroc, Casablanca, Morocco

    Hicham Charoute

  5. In vitro Fertilization Center IRIFIV, Iris Clinic, Casablanca, Morocco

    Noureddine Louanjli

Authors
  1. Salaheddine Redouane
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  2. Houda Harmak
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  3. Adil El Hamouchi
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  4. Hicham Charoute
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  5. Noureddine Louanjli
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  6. Abderrahim Malki
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  7. Abdelhamid Barakat
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  8. Hassan Rouba
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Contributions

Salaheddine Redouane: Conceptualization, data collection, bioinformatic analysis, writing. Houda Harmak: Review and enhancements of the writing. Adil El Hamouchi and Hicham Charoute: Sequencing and bioinformatic analysis coordination. Noureddine Louanjli: Supervision during the recruitment process of the patient. Abderrahim Malki: Academic supervision and reviewing. Abdelhamid Barakat and Hassan Rouba: Technical supervision and reviewing.

Corresponding author

Correspondence to Salaheddine Redouane.

Ethics declarations

Ethical approval

This study was approved by the Biomedical Research Ethics Committee at the Faculty of Medicine and Pharmacy, Casablanca, Morocco (approval number: 05/2022). We confirm that all research work in this study complies with ethical guidelines, including adherence to the legal requirements of the study country.

Consent to participate

Informed consent was obtained from the recruited participant.

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Patient signed an informed consent form for the publication of his data.

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The authors declare no competing interests.

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Redouane, S., Harmak, H., El Hamouchi, A. et al. Whole exome sequencing reveals ABCD1 variant as a potential contributor to male infertility. Mol Biol Rep 52, 148 (2025). https://doi.org/10.1007/s11033-025-10234-7

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