Interdisciplinary Group for the Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (UNICAMP), Campinas, Brazil.
Department of Pediatrics, State University of Campinas (UNICAMP), Campinas, Brazil.
Sex Dev. 2022;16(4):242-251. doi: 10.1159/000526036. Epub 2023 Jan 19.
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.
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.
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).
The etiology of most 46,XX OT-DSD cases remains elusive, highlighting the importance of a deeper molecular investigation.
卵睾性性发育障碍（OT-DSD）是一种罕见的疾病，其定义为在同一个个体中同时存在睾丸组织和卵巢组织（含有卵泡）。在 SRY 阴性 46,XX OT-DSD 中，睾丸组织的存在可能是由于 NR5A1 的变异。我们的目的是在 SRY 阴性 46,XX OT-DSD 患者中寻找 NR5A1 变体，并对 NR5A1 变异对 46,XX OT-DSD 的贡献进行系统评价。
对 7 例 SRY 阴性 46,XX OT-DSD 患者（5 例单纯病例和 2 例另一个有 46,XX DSD 同胞的患者）进行 NR5A1 测序。根据 PRISMA-P 指南对 NR5A1 测序的 46,XX OT-DSD 患者的原始研究进行系统评价。选择病例报告进行临床特征分析。未包括与 NR5A1 相关的睾丸 DSD 个体。
NR5A1 测序未在我们的患者中发现致病性变异。我们的队列包含在这项系统评价中，还有另外 7 篇文章，总共包括 56 例通过 Sanger 或全外显子组测序研究的 46,XX OT-DSD 患者。其中，发现了 3 个 NR5A1 致病性变异（占病例的 5%）。对这 3 例和 5 例病例报告的临床分析显示：16 个性腺中，卵睾的比例较高（13/16），双侧 OT-DSD（5/8 例）。
大多数 46,XX OT-DSD 病例的病因仍然难以捉摸，这突出了更深入的分子研究的重要性。
