دورية أكاديمية
Identification of a novel homozygous NR5A1 variant in a patient with a 46,XY disorders of sex development.
العنوان: | Identification of a novel homozygous NR5A1 variant in a patient with a 46,XY disorders of sex development. |
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المؤلفون: | Kırkgöz T; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Gürsoy S; Deparment of Paediatric Genetics, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Acar S; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Köprülü Ö; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Özkaya B; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Arslan G; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Nalbantoğlu Ö; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Hazan F; Department of Medical Genetics, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye., Özkan B; Division of Paediatric Endocrinology, Behçet Uz Children's Education and Research Hospital, Izmir, Türkiye. |
المصدر: | Journal of pediatric endocrinology & metabolism : JPEM [J Pediatr Endocrinol Metab] 2024 Apr 23; Vol. 37 (6), pp. 575-579. Date of Electronic Publication: 2024 Apr 23 (Print Publication: 2024). |
نوع المنشور: | Case Reports; Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Walter de Gruyter Country of Publication: Germany NLM ID: 9508900 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2191-0251 (Electronic) Linking ISSN: 0334018X NLM ISO Abbreviation: J Pediatr Endocrinol Metab Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Mar. 2011- : Berlin : Walter de Gruyter Original Publication: London : Freund Pub. House, [1995- |
مواضيع طبية MeSH: | Steroidogenic Factor 1*/genetics , Disorder of Sex Development, 46,XY*/genetics , Homozygote*, Humans ; Female ; Male ; Infant ; Mutation ; Prognosis |
مستخلص: | 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. (© 2024 Walter de Gruyter GmbH, Berlin/Boston.) |
References: | Kirkgoz, T, Guran, T. Primary adrenal insufficiency in children: diagnosis and management. Best Pract Res Clin Endocrinol Metabol 2018;32:397–424. https://doi.org/10.1016/j.beem.2018.05.010 . (PMID: 10.1016/j.beem.2018.05.010) Werner, R, Mönig, I, Lünstedt, R, Wünsch, L, Thorns, C, Reiz, B, et al.. New NR5A1 pathogenic variants and phenotypic variations of gonadal dysgenesis. PLoS One 2017;12:e0176720. https://doi.org/10.1371/journal.pone.0176720 . (PMID: 10.1371/journal.pone.0176720) Fabbri-Scallet, H, de Sousa, LM, Maciel-Guerra, AT, Guerra-Júnior, G, de Mello, MP. Pathogenic variant update for the NR5A1 gene involved in DSD and infertility. Hum Mutat 2020;41:58–68. https://doi.org/10.1002/humu.23916 . (PMID: 10.1002/humu.23916) Luo, X, Ikeda, Y, Schlosser, DA, Parker, KL. Steroidogenic factor 1 is the essential transcript of the mouse Ftz-F1 gene. Mol Endocrinol 1995;9:1233–9. https://doi.org/10.1210/mend.9.9.7491115 . (PMID: 10.1210/mend.9.9.7491115) Achermann, JC, Ozisik, G, Ito, M, Orun, UA, Harmanci, K, Gurakan, B, et al.. Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner. J Clin Endocrinol Metab 2002;87:1829–33. https://doi.org/10.1210/jc.87.4.1829 . (PMID: 10.1210/jc.87.4.1829) Lourenço, D, Brauner, R, Lin, L, De Perdigo, A, Weryha, G, Muresan, M, et al.. Pathogenic variants in NR5A1 associated with ovarian insufficiency. N Engl J Med 2009;360:1200–10. https://doi.org/10.1056/nejmoa0806228 . (PMID: 10.1056/nejmoa0806228) Soardi, FC, Coeli, FB, Maciel-Guerra, AT, Guerra-Júnior, G, Mello, MP. Complete XY gonadal dysgenesis due to p.D293N homozygous pathogenic variant in the NR5A1 gene: a case study. J Appl Genet 2010;51:223–4. https://doi.org/10.1007/bf03195733 . (PMID: 10.1007/bf03195733) Zangen, D, Kaufman, Y, Banne, E, Weinberg-Shukron, A, Abulibdeh, A, Garfinkel, BP, et al.. Testicular differentiation factor SF-1 is required for human spleen development. J Clin Invest 2014;124:2071–5. https://doi.org/10.1172/jci73186 . (PMID: 10.1172/jci73186) Guran, T, Buonocore, F, Saka, N, Ozbek, MN, Aycan, Z, Bereket, A, et al.. Rare causes of primary adrenal insufficiency: genetic and clinical characterization of a large nationwide cohort. J Clin Endocrinol Metab 2016;101:284–92. https://doi.org/10.1210/jc.2015-3250 . (PMID: 10.1210/jc.2015-3250) Cools, M, Grijp, C, Neirinck, J, Tavernier, SJ, Schelstraete, P, Van De Velde, J, et al.. Spleen function is reduced in individuals with NR5A1 variants with or without a difference of sex development: a cross-sectional study. Eur J Endocrinol 2024;190:34–43. https://doi.org/10.1093/ejendo/lvad174 . (PMID: 10.1093/ejendo/lvad174) Richards, S, Aziz, N, Bale, S, Bick, D, Das, S, Gastier-Foster, J, et al.., ACMG Laboratory Quality Assurance Committee . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–24. https://doi.org/10.1038/gim.2015.30 . (PMID: 10.1038/gim.2015.30) Baetens, D, Stoop, H, Peelman, F, Todeschini, AL, Rosseel, T, Coppieters, F, et al.. NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development. Genet Med 2017;19:367–76. https://doi.org/10.1038/gim.2016.118 . (PMID: 10.1038/gim.2016.118) Lenti, E, Farinello, D, Yokoyama, KK, Penkov, D, Castagnaro, L, Lavorgna, G, et al.. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development. J Clin Invest 2016;126:2452–64. https://doi.org/10.1172/jci82956 . (PMID: 10.1172/jci82956) Colson, C, Aubry, E, Cartigny, M, Rémy, AA, Franquet, H, Leroy, X, et al.. SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1-mutated patient’s management. Clin Genet 2017;92:99–103. https://doi.org/10.1111/cge.12957 . (PMID: 10.1111/cge.12957) |
فهرسة مساهمة: | Keywords: DSD 46 XY; NR5A1; ambiguous genitalia; hyposplenism |
المشرفين على المادة: | 0 (Steroidogenic Factor 1) 0 (NR5A1 protein, human) |
تواريخ الأحداث: | Date Created: 20240423 Date Completed: 20240605 Latest Revision: 20240709 |
رمز التحديث: | 20240709 |
DOI: | 10.1515/jpem-2023-0551 |
PMID: | 38650427 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2191-0251 |
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DOI: | 10.1515/jpem-2023-0551 |