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Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I

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Abstract

Purpose

Leydig cell hypoplasia is a rare autosomal recessive 46,XY disorder of sexual development (DSD). It is caused by homozygous or compound heterozygous inactivating mutations in the human luteinizing hormone/chorionic gonadotropin hormone receptor (LHCGR) gene. In Leydig cell hypoplasia type I, patients are characterized by predominantly female external genitalia, which usually go unrecognized until the age of puberty.

Methods

This study reports three patients descending from two unrelated families. We performed clinical, hormonal, histopathological, molecular, and bioinformatics studies for the studied cases.

Results

All investigations suggested 46,XY DSD and Leydig cell hypoplasia. Molecular analysis showed two novel homozygous inactivating mutations (p.Glu148Ter and p.Leu104Pro) within the extracellular domain of the LHCGR gene.

Conclusion

Although the mutations of the LHCGR gene are distributed heterogeneously, without hotspot or recurrent mutations, about one fifth of the reported mutations worldwide have been detected in Arab patients. This is probably due to the high consanguinity rate in these populations, which increases the percentage of autosomal recessive disorders and the homozygous LHCGR gene mutations.

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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgments

The authors thank all the patients and families who contributed samples to this study and consented to have their data shared.

Funding

The research was funded by the National Research Centre (NRC), Egypt, through the project titled “Molecular assessment to identify the frequency of 46,XY disorders of sex development (DSD) among children and adolescents”, grant number: 12060179.

Author information

Authors and Affiliations

  1. Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, 33 El Buhouth St., Dokki, Cairo, 12311, Egypt

    Heba Amin Hassan & M. L. Essawi

  2. Human Cytogenetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

    M. K. Mekkawy

  3. Clinical Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

    I. Mazen

Authors
  1. Heba Amin Hassan
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  2. M. L. Essawi
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  3. M. K. Mekkawy
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  4. I. Mazen
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Contributions

All the authors have read and approved the manuscript, and all the authors contributed equally.

Corresponding author

Correspondence to Heba Amin Hassan.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Medical Research Ethics Committee (MREC) of the National Research Centre [registration number: 19-179].

Informed consent

Written informed consent was obtained from all individual participants included in the study according to the Medical Research Ethics Committee (MREC) of the NRC.

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Informed written consents were taken from patients, their legal guardians and their parents approving the publishing of their medical and personal information.

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Hassan, H.A., Essawi, M.L., Mekkawy, M.K. et al. Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I. Hormones 19, 573–579 (2020). https://doi.org/10.1007/s42000-020-00226-6

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  • DOI: https://doi.org/10.1007/s42000-020-00226-6

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