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

IF 2.4 4区医学 Q2 DEVELOPMENTAL BIOLOGY

Sexual Development Pub Date : 2022-01-01 DOI:10.1159/000526036

Beatriz Amstalden Barros, Mara Sanches Guaragna, Helena Fabbri-Scallet, Maricilda Palandi de Mello, Gil Guerra-Júnior, Andréa Trevas Maciel-Guerra

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引用次数: 0

Abstract

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.

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NR5A1变异是46,xx性发育卵睾丸障碍的常见原因吗?单中心分析与系统评价。

卵睾丸性发育障碍(ovotesular disorder of sex development, 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)同时出现而定义。在sry阴性46,XX OT-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46,xx例sry阴性OT-DSD患者中寻找NR5A1变异，并对NR5A1变异对46,xx例OT-DSD的贡献进行系统回顾。方法:对7例sry阴性46,XX OT-DSD患者进行NR5A1 Sanger测序，其中5例为单纯性病例，2例伴有兄弟姐妹46,XX DSD。根据PRISMA-P指南对46,xx例OT-DSD患者NR5A1测序的原始研究进行系统评价。选取病例报告进行临床特征分析。未纳入nr5a1相关睾丸DSD患者。结果:在我们的患者中，NR5A1的Sanger测序未显示致病变异。我们的队列与其他7篇文章被纳入本系统综述，通过Sanger或全外显子组测序调查的OT-DSD患者共566xx例。从中鉴定出3种NR5A1致病变异(占病例的5%)。3例临床分析及5例报告显示:以卵睾丸为主(13/16)，双侧OT-DSD为主(5/8)。结论:大多数46,xx例OT-DSD的病因仍然难以捉摸，强调了更深入的分子研究的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Sexual Development 生物-发育生物学

CiteScore

4.00

自引率

4.30%

发文量

审稿时长

>12 weeks

期刊介绍： Recent discoveries in experimental and clinical research have led to impressive advances in our knowledge of the genetic and environmental mechanisms governing sex determination and differentiation, their evolution as well as the mutations or endocrine and metabolic abnormalities that interfere with normal gonadal development. ‘Sexual Development’ provides a unique forum for this rapidly expanding field. Its broad scope covers all aspects of genetics, molecular biology, embryology, endocrinology, evolution and pathology of sex determination and differentiation in humans and animals. It publishes high-quality original research manuscripts, review articles, short reports, case reports and commentaries. An internationally renowned and multidisciplinary editorial team of three chief editors, ten prominent scientists serving as section editors, and a distinguished panel of editorial board members ensures fast and author-friendly editorial processing and peer reviewing.