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Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility

  • Genetics
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To identify the contribution of mutations in the Desert Hedgehog (DHH) gene to the disorders of sexual differentiation (DSD) and male infertility.

Methods

The study included a total 430 subjects, including 47 gonadal dysgenesis cases, 6 patients with undescended testis and infertility characterized by azoospermia, 125 infertile male patients characterized by oligoasthenozoospermia, 24 patients with oligoasthenoteratozoospermia, and 200 ethnically matched normozoospermic fertile men who had fathered a child in the last two years. Sequencing of the complete coding region of the DHH gene was undertaken to find its contribution to the DSD and male infertility.

Results

We observed four novel mutations in the DHH gene in the cases with different reproductive anomalies. A synonymous substitution, c. 543C>T (p.His181His) was observed in 6.6% oligoasthenozoospermic infertile males and 1.5% normozoospermic fertile control samples (RR = 4.4077, 95%CI 1.19–16.29). Another synonymous substitution, c.990G>A (p.Ala330Ala) was observed in an infertile patient with unilateral undescended testis (case #12). Insertion of G at c.1156insG (p.Arg385fs) was observed in a case with bilateral undescended testis and azoospermia (case #23). In gonadal dysgenesis category, two mutations, insertion of G at c.1156insG (p.Arg385fs) and c.997A>G (p.Thr333Ala) substitution were observed in one case (case #34). These mutations were completely absent in control samples.

Conclusion

Mutations in the DHH gene impact reproduction with mild mutations affecting fertility, and severe or multiple mutations resulting in gonadal dysgenesis.

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Acknowledgements

The authors are thankful to the participants and their families. The authors would like to thank the Council of Scientific and Industrial Research (CSIR) for funding under network scheme of projects (BSC0101). PM is thankful to the University Grants Commission (UGC) for the financial support (Ref no. 460/CSIR-UGC NET DEC.2017).

Funding

The study was financially supported by the Council of Scientific and Industrial Research (CSIR) under network scheme of projects (BSC0101).

Author information

Authors and Affiliations

  1. Division of Endocrinology, Central Drug Research Institute, Lucknow, India

    Poonam Mehta & Singh Rajender

  2. Academy of Scientific and Industrial Research (AcSIR), Ghaziabad, India

    Poonam Mehta, Kumarasamy Thangaraj & Singh Rajender

  3. Centre for Cellular and Molecular Biology, Hyderabad, India

    Priyamvada Singh & Kumarasamy Thangaraj

  4. Institute of Reproductive Medicine, Kolkata, India

    Nalini J. Gupta & Baidyanath Chakravarty

  5. King George’s Medical University, Lucknow, India

    Satya Narayan Sankhwar

  6. Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India

    Kumarasamy Thangaraj

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  1. Poonam Mehta
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  2. Priyamvada Singh
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Correspondence to Singh Rajender.

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The study was approved by the Institutional Human Ethics Committee (IHEC) of the Central Drug Research Institute, Lucknow. Informed consent was obtained from all the individual participants included in the study.

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Mehta, P., Singh, P., Gupta, N.J. et al. Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility. J Assist Reprod Genet 38, 1871–1878 (2021). https://doi.org/10.1007/s10815-021-02140-1

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