Xia Junke, Wu Jing, Chen Chen, Zhao Zhenhua, Xie Yanchuan, Bai Zhouxian, Kong Xiangdong
Center of Genetic and Prenatal Diagnosis, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Gynecol Endocrinol. 2021 Oct;37(10):934-940. doi: 10.1080/09513590.2021.1960307. Epub 2021 Aug 2.
The rare condition 46, XY disorders of sex development (DSDs) is characterized by the female phenotype and male karyotype. We aimed to describe the genetic basis of 46, XY DSDs in nine patients and the genotype-phenotype relationships of the genes involved.
Targeted next-generation sequencing (NGS) was used to analyze the underlying hereditary etiology in nine female patients with 46, XY DSDs. analyses were used to predict the effects of novel variants on the protein function of the identified genes.
Primary amenorrhea with the absence of puberty, inguinal hernia, and clitoridauxe were common complaints. All enrolled patients had a differential etiology by genetic testing, and five novel genetic variants involved in four genes (, , , and ) were identified. A novel nonsense variant of c.51C > G was found in XY patients without testicles. Two novel heterozygous variants, i.e. c.265A > T (Ile89Leu) and c.422T > C (Val141Ala), of the gene were found in male pseudo-hermaphroditism.
We expanded the genetic mutation spectrum and described in detail the genotype-phenotype relationships of 46, XY DSDs. DNA sequencing for should be a priority in female patients with 46, XY DSDs. NGS is useful for clarifying genetic pathogenesis and could provide a basis for clinical diagnosis and treatments of patients with 46, XY DSDs.
罕见的46，XY性发育障碍（DSDs）以女性表型和男性核型为特征。我们旨在描述9例患者中46，XY DSDs的遗传基础以及所涉及基因的基因型-表型关系。
采用靶向二代测序（NGS）分析9例46，XY DSDs女性患者潜在的遗传病因。 分析用于预测新变异对所鉴定基因蛋白质功能的影响。
主要症状为原发性闭经伴青春期缺失、腹股沟疝和阴蒂增大。所有纳入患者经基因检测均有不同病因，共鉴定出涉及4个基因（ 、 、 和 ）的5个新的遗传变异。在无睾丸的XY患者中发现了 基因的一个新的c.51C＞G无义变异。在男性假两性畸形中发现了 基因的两个新的杂合变异，即c.265A＞T（Ile89Leu）和c.422T＞C（Val141Ala）。
我们扩展了基因突变谱，并详细描述了46，XY DSDs的基因型-表型关系。对于46，XY DSDs女性患者， 基因的DNA测序应作为首要检查。NGS有助于阐明遗传发病机制，并可为46，XY DSDs患者的临床诊断和治疗提供依据。
