Phenotype and genetic characteristics in 20 Chinese patients with 46,XY disorders of sex development
Phenotype and genetic characteristics in 20 Chinese patients with 46,XY disorders of sex development
复制标题
DOI：
10.1007/s40618-023-02020-8
复制
发表时间：
2023-02-06
影响因子：
5.4
通讯作者：
He，R.
中科院分区：
文献类型：
--
作者：
Zheng，G. Y.;Chu，G. M.;He，R.
目的46，XY 性发育障碍 (DSD) 是最复杂和最常见的 DSD 类型。迄今为止，已鉴定出 30 多个与 46,XY DSD 相关的基因。然而，由于高度的遗传和临床异质性，46,XY DSD 的突变谱并不完整。本研究旨在提供18例中国46,XY DSD患者的临床和突变特征。方法共招募20名无关的46,XY DSD个体。采用全外显子组测序（WES）或定制组合测序结合桑格测序来检测致病突变。根据美国医学遗传学与基因组学学院（ACMG）指导意见以及ACMG和临床基因组资源（ClinGen）推荐的技术标准评估该变异的致病性。结果6名患者携带NR5A1突变；两名患者携带 NR0B1 突变；六名患者携带SRD5A2突变；六名患者携带 AR 突变。鉴定出涉及三个基因（NR5A1、NR0B1 和 AR）的 6 个新的遗传变异。结论我们确定了所有入组患者的遗传病因。我们的研究扩大了46,XY DSD的突变谱，为未来具有相同突变的患者提供了诊断依据。
Purpose46,XY disorders of sex development (DSD) is the most complicated and common type of DSD. To date, more than 30 genes have been identified associated with 46,XY DSD. However, the mutation spectrum of 46,XY DSD is incomplete owing to the high genetic and clinical heterogeneity. This study aims to provide clinical and mutational characteristics of 18 Chinese patients with 46,XY DSD.MethodsA total of 20 unrelated individuals with 46,XY DSD were recruited. Whole-exome sequencing (WES) or custom-panel sequencing combined Sanger sequencing were performed to detect the pathogenic mutations. The pathogenicity of the variant was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidance and technical standards recommended by the ACMG and the Clinical Genome Resource (ClinGen).ResultsSix patients harboredNR5A1mutations; two patients harboredNR0B1mutations; six patients harboredSRD5A2mutations; six patients harboredARmutations. Six novel genetic variants were identified involved in three genes (NR5A1,NR0B1,andAR).ConclusionWe determined the genetic etiology for all enrolled patients. Our study expanded the mutation spectrum of 46,XY DSD and provided diagnostic evidence for patients with the same mutation in the future.