Abstract：
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.
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.
摘要：
背景：卵巢性发育障碍（OT-DSD）是一种罕见的疾病，由同一个体的睾丸组织和卵巢组织（含卵泡）的伴随性定义。在SRY-阴性46，XXOT-DSD中，睾丸组织的存在可能是由于NR5A1的变化。我们的目的是在SRY阴性的46，XXOT-DSD患者中寻找NR5A1变体，并对NR5A1变体对46，XXOT-DSD的贡献进行系统评价。
方法：对7例SRY阴性46，XXOT-DSD患者进行了NR5A1的Sanger测序：5例单纯病例，2例同胞46，XXDSD。根据PRISMA-P指南，对46例XXOT-DSD患者的NR5A1测序原始研究进行了系统评价。选择病例报告进行临床特征分析。不包括NR5A1相关睾丸DSD的个体。
结果：NR5A1的Sanger测序没有发现我们患者的致病变异。我们的队列与其他七篇文章一起纳入了这篇系统综述，通过Sanger或全外显子组测序对5646名XXOT-DSD患者进行了调查。从他们那里,发现了3种NR5A1致病变种(5%的病例)。对这3例病例和5例病例报告的临床分析显示：卵睾丸占优势（13/16性腺）和双侧OT-DSD（5/8例）。
结论：大多数46例XXOT-DSD病例的病因仍然难以捉摸，强调更深入的分子研究的重要性。
方法：对7例SRY阴性46，XXOT-DSD患者进行了NR5A1的Sanger测序：5例单纯病例，2例同胞46，XXDSD。根据PRISMA-P指南，对46例XXOT-DSD患者的NR5A1测序原始研究进行了系统评价。选择病例报告进行临床特征分析。不包括NR5A1相关睾丸DSD的个体。
结果：NR5A1的Sanger测序没有发现我们患者的致病变异。我们的队列与其他七篇文章一起纳入了这篇系统综述，通过Sanger或全外显子组测序对5646名XXOT-DSD患者进行了调查。从他们那里,发现了3种NR5A1致病变种(5%的病例)。对这3例病例和5例病例报告的临床分析显示：卵睾丸占优势（13/16性腺）和双侧OT-DSD（5/8例）。
结论：大多数46例XXOT-DSD病例的病因仍然难以捉摸，强调更深入的分子研究的重要性。
