Identification of a novel homozygous NR5A1 variant in a patient with a 46,XY disorders of sex development
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Tarık Kırkgöz
Abstract
Objectives
Nuclear receptor subfamily 5 group A member 1 (NR5A1) is a transcription factor critical for the development of various organs. Pathogenic variants in NR5A1 are associated with a spectrum of disorders of sex development (DSD).
Case presentation
A 15-month-old baby, raised as a girl, was referred for genital swelling and ambiguous genitalia. Born to healthy consanguineous parents, the baby had a phallus, perineal hypospadias, labial fusion, and a hypoplastic scrotum. Hormonal evaluation showed normal levels, and ultrasonography revealed small gonads and absence of Müllerian derivatives. Post-human chorionic gonadotropin (hCG) testing indicated an adequate testosterone response. The karyotype was 46,XY, and in it was found a homozygous NR5A1 variant (c.307 C>T, p.Arg103Trp) in a custom 46 XY DSD gene panel. Notably, the patient exhibited complete sex reversal, hyposplenia, and no adrenal insufficiency.
Conclusions
Previously, NR5A1 pathogenic variants were considered to be dominantly inherited, and homozygous cases were thought to be associated with adrenal insufficiency. Despite the homozygous pathogenic variant, our patient showed hyposplenism with normal adrenal function; this highlights the complexity of NR5A1 genotype–phenotype correlations. These patients should be monitored for adrenal insufficiency and DSD as well as splenic function.
Acknowledgments
The authors wish to express their gratitude to parents and the patients who participated in this study.
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Research ethics: The local Institutional Review Board deemed the study exempt from review.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Research funding: None declared.
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Data availability: The raw data can be obtained on request from the corresponding author.
References
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- Frontmatter
- Original Articles
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- Exploring ketoacidosis frequency and risk factors in childhood-onset type 1 diabetes: an 8-year retrospective study (2011–2018) at a tertiary paediatric hospital in Tripoli, Libya
- Automated insulin delivery in children with type 1 diabetes during physical activity: a meta-analysis
- Association between maternal and cord blood thyroid hormones, and urine iodine concentration with fetal growth
- Post hoc subgroup analysis of Asian children with paediatric GHD from the global phase 3 efficacy and safety study of once-weekly somatrogon vs. once-daily somatropin
- Familial dysalbuminemic hyperthyroxinemia (FDH) due to Arg242 His variant in ALB gene in Turkish children
- A novel useful marker in the early discrimination of transient hyperthyrotropinemia/hypothyroxinemia and congenital hypothyroidism in preterm infants: thyroid-stimulating hormone/free thyroxine ratio
- Comprehensive analyses of phenylalanine hydroxylase variants and phenotypic characteristics of patients in the eastern region of Türkiye
- Relationship between urinary sodium excretion and bone mineral density in pediatrics: population-based study from KNHANES V 2010–2011
- Trajectory of the body mass index of children and adolescents attending a reference mental health center
- Case Reports
- Prenatal presentation of a hyperfunctioning thyroid nodule
- A very rare presentation of mitochondrial elongation factor Tu deficiency-TUFM mutation and literature review
- Identification of a novel homozygous NR5A1 variant in a patient with a 46,XY disorders of sex development
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