Are NR5A1 Variations a Frequent Cause of 46,XX Ovotesticular Disorders of Sex Development? Analysis from a Single Center and Systematic Review

Autor(es)

Barros, Beatriz Amstalden ; Guaragna, Mara Sanches ; Fabbri-Scallet, Helena ; de Mello, Maricilda Palandi ; Guerra-Junior, Gil ; Maciel-Guerra, Andrea Trevas

• Tipo de documento: Artigo Científico
• Fonte: SEXUAL DEVELOPMENT; v. 16, n. 4, p. 10-pg., 2023-02-01.

Resumo

Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition defined by concomitance of testicular tissue and ovarian tissue (containing follicles) in the same individual. In SRY-negative 46,XX OT-DSD, the presence of testicular tissue may be due to variations in NR5A1. Our aims were to search for NR5A1 variants in SRY-negative 46,XX OT-DSD patients and to perform a systematic review on the contribution of NR5A1 variations to 46,XX OT-DSD. Methods: Sanger sequencing of NR5A1 was performed in seven SRY-negative 46,XX OT-DSD patients: five simplex cases and two with another sibling with a 46,XX DSD. Systematic review of original studies on NR5A1 sequencing of 46,XX OT-DSD patients was performed according to PRISMA-P guideline. Case reports were selected for analysis of clinical features. Individuals with NR5A1-associated testicular DSD were not included. Results: Sanger sequencing of NR5A1 did not reveal pathogenic variants among our patients. Our cohort was included in this systematic review with seven other articles, totalizing fifty-six 46,XX OT-DSD patients investigated by Sanger or whole-exome sequencing. From them, three NR5A1 pathogenic variants were identified (5% of the cases). Clinical analysis of these 3 cases and 5 case reports revealed: predominance of ovotestis (13/16 gonads) and bilateral OT-DSD (5/8 cases). Conclusion: The etiology of most 46,XX OT-DSD cases remains elusive, highlighting the importance of a deeper molecular investigation. (AU)

• Processo FAPESP: 19/26382-3 - Aplicação de técnicas de genética molecular e de análise da expressão gênica ao estudo do distúrbio da diferenciação do sexo ovário-testicular
• Beneficiário: Andrea Trevas Maciel Guerra
• Modalidade de apoio: Auxílio à Pesquisa - Regular