Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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The rare case of 46,XX testicular disorder of sex development carrying a heterozygous p.Arg92Trp variant in NR5A1

  • Lia Kim (Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital) ;
  • Hwa Young Kim (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Jung Min Ko (Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital)
  • Received : 2022.10.11
  • Accepted : 2022.12.20
  • Published : 2022.12.31
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Abstract

The 46,XX testicular disorder of sex development (DSD) is a rare condition in which 46,XX individuals develop testicular differentiation and virilization. Translocation of the sex-determining region Y (SRY) onto the X chromosome is the main cause of 46,XX testicular DSD, whereas dysregulation between pro-testis and pro-ovarian genes can induce SRY-negative 46,XX testicular DSD. Nuclear receptor subfamily 5 group A member 1 (NR5A1), a nuclear receptor transcription factor, plays an essential role in gonadal development in XY and XX embryos. Herein, we report the first Korean case of SRY-negative 46,XX testicular DSD with a heterozygous NR5A1 p.Arg92Trp variant. The patient presented with a small penis, bifid scrotum, and bilateral undescended testes. Whole exome sequencing revealed a heterozygous missense variant (c.274C>T) of NR5A1. Our case highlights that NR5A1 gene variants need to be considered important causative factors of SRY-negative non-syndromic 46,XX testicular DSD.

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References

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