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Expanding the phenotype of copy number variations involving NR0B1 (DAX1)

European Journal of Human Genetics volume 32, pages 421–425 (2024)Cite this article

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Abstract

46,XY gonadal dysgenesis (GD) is a disorder of sex development due to incomplete gonadal differentiation into testes, resulting in female to ambiguous external genitalia. Duplications at the Xp21.2 locus involving the NR0B1 (DAX1) gene have previously been associated with 46,XY GD. More recently, a complex structural variant not directly involving NR0B1 has been reported in 46,XY GD illustrating that the mechanism of how copy number variants (CNVs) at Xp21.2 may cause 46,XY gonadal dysgenesis is not yet fully understood. Here, we report on three families in which a duplication involving the NR0B1 gene was detected in the context of prenatal screening. This is the first report of duplications involving NR0B1 in three phenotypically normal males in two families. Fertility problems were present in one adult male carrier. The data reported here from an unbiased screening population broaden the phenotype associated with CNVs involving NR0B1, and this may aid clinicians in counseling and decision making in the prenatal context.

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Fig. 1: Pedigrees of the three families described here.
Fig. 2: UCSC plot of the Xp21.2 CNVs detected in the three families described here (A.I1, B.I2, C.I2) and those reported earlier.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We thank the patients and their families who participated in this study.

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Authors and Affiliations

  1. Center for Human Genetics, University Hospitals Leuven-KU Leuven, Leuven, Belgium

    Nathalie Veyt, Griet Van Buggenhout, Koen Devriendt, Kris Van Den Bogaert & Nathalie Brison

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  1. Nathalie Veyt
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  2. Griet Van Buggenhout
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  3. Koen Devriendt
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  4. Kris Van Den Bogaert
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  5. Nathalie Brison
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Contributions

Conceptualization: NV, GVB, KD, KVDB, NB. Visualization: NV. Writing original manuscript: NV. Supervision: GVB, KD, KVDB, NB

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Correspondence to Nathalie Veyt.

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The authors declare no competing interests.

Ethical approval

This study is approved by the Ethics Committee Research of University Hospitals Leuven (S67531). In compliance with the Declaration of Helsinki, written informed consent was obtained from all patients who participated in this study.

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Veyt, N., Van Buggenhout, G., Devriendt, K. et al. Expanding the phenotype of copy number variations involving NR0B1 (DAX1). Eur J Hum Genet 32, 421–425 (2024). https://doi.org/10.1038/s41431-023-01522-6

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