46,ΧΥ DSD in an adolescent with a novel de novo variant of the NR5A1 gene - case report and literature review.

Autor: Kostopoulou E; Department of Pediatrics, University Hospital of Patras, Patras, Greece. irekost@upatras.gr.; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, School of Medicine, University of Patras, Patras, 26500, Greece. irekost@upatras.gr., Eliades A; Intensive Care Unit, University Hospital of Patras, Patras, Greece., Papatheodoropoulou A; Intensive Care Unit, University Hospital of Patras, Patras, Greece., Sertedaki A; Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece., Sinopidis X; Department of Pediatrics, University Hospital of Patras, Patras, Greece., Tzelepi V; Department of Pathology, School of Medicine, University of Patras, Patras, 26504, Greece., Jang S; 3Billion inc, Seoul, Republic of Korea., Seo GH; 3Billion inc, Seoul, Republic of Korea., Chrysis D; Department of Pediatrics, University Hospital of Patras, Patras, Greece.; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, School of Medicine, University of Patras, Patras, 26500, Greece.
Jazyk: angličtina
Zdroj: Hormones (Athens, Greece) [Hormones (Athens)] 2024 Jul 25. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1007/s42000-024-00589-0
Abstrakt: Purpose: In addition to chromosomal abnormalities, several genes have been implicated as causes of disorders of sex development (DSD). The NR5A1 gene expresses SF1, a transcription factor that plays a role in steroidogenesis by controlling multiple stages of adrenal and gonadal development, its mutations having been reported in cases of DSD.
Case Presentation: A 15-year-old teenager was admitted to the Children's ICU of a tertiary center due to acute encephalitis. On physical examination, labia majora and minora, open vaginal opening, and a 4.8 cm phallus (stretched length) in the anatomical position of the clitoris were identified. The patient also presented with hirsutism, breast development was Tanner stage I, and pubic hair was Tanner V. Medical history revealed primary amenorrhea. Imaging studies revealed oval formations primarily compatible with testicular parenchyma in the anatomical location of the inguinal ducts. The karyotype identified a 46,XY individual, while whole exome sequencing (WES) revealed the presence of a heterozygous pathogenic splice site variant of the NR5A1 gene (NM_004959.5), c.990G > C, p.Glu330Asp, which, on further genetic testing of the parents, was proven to be de novo. According to psychiatric assessment, the patient self-identifies as a female. Laparoscopic exploration showed no residual Mullerian ducts or the presence of testicular tissue. A gonadectomy was performed and hormone replacement therapy with estrogens was initiated.
Conclusion: We describe a rare case of 46,XY DSD in an phenotypically female adolescent carrying the novel de novo p.Glu330Asp variant of the NR5A1 gene. We also highlight the frequent delay in diagnosis of ambiguous external genitalia.
(© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)
Databáze: MEDLINE
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