Clinical Original Article
Molecular diagnosis and clinical features of 206 patients with 46, XY disorders of sexual development
Liu Xuemeng, Zhao Shuangxia, Zhu Hui, Han Bing, Xu Yue, Yao Haijun, Liu Yang, Chen Yan, Cheng Kaixiang, Song Huaidong, Qiao Jie
Published 2022-09-25
Cite as Chin J Endocrinol Metab, 2022, 38(9): 781-788. DOI: 10.3760/cma.j.cn311282-20220219-00094
Abstract
ObjectiveTo investigate methods of molecular diagnosis and clinical features of 46, XY disorders of sexual development(DSD).
MethodsA total of 206 cases of 46, XY DSD patients, who visited the Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, from July 2009 to June 2021, underwent AA chip based on multiplex PCR and probe-capture-targeted next-generation sequencing. Clinical features of patients with genetic diagnosis were analyzed.
ResultsAmong 206 patients, the diagnostic rate of patients with micropenis, hypospadias and cryptorchidism was the highest, up to 75.28%. Almost all patients had different degrees of undermasculinized external genitalia. The most frequent phenotype was micropenis with hypospadias(87.25%). Only one gene variant was detected in 81 patients(39.32%), multiple genetic variants were detected in 104 patients(50.49%), and no gene variant was identified in 21 patients(10.19%). 107 patients had definite genetic diagnosis, with a diagnostic rate of 51.94% by adding the pathogenic and likely pathogenic ratios following the American College of Medical Genetics and Genomics(ACMG) guidelines, including 40 patients of steroid 5α-reductase type 2(SRD5A2) variants(37.38%), 36 patients of androgen receptor(AR) variants(33.64%), 13 patients of steroidogenic factor 1(NR5A1) variants(16.82%), 6 patients of 17β-hydroxysteroid dehydrogenases 3(HSD17B3) variants(5.61%), 2 patients of 17α-hydroxylase/17, 20-lyase enzyme(CYP17A1), Wilms′ tumor 1(WT1) and GATA binding protein 4(GATA4) variants(1.87%), and one patient of luteinizing hormone receptor(LHCGR) variant(0.93%). Gynecomastia was found in 29 of 81 postpubertal patients, of which 25(86.21%) had AR variants.
Conclusions46, XY DSD presents complex clinical manifestations and molecular etiologies. Targeted nextgeneration sequencing has the advantages of high throughput, high efficiency and low cost, which has a high value especially in etiological diagnosis of 46, XY DSD with large genetic heterogeneity.
Key words:
Disorders of sex development; 46, XY disorders of sexual development; Targeted next-generation sequencing; Molecular diagnosis
Contributor Information
Liu Xuemeng
Department of Endocrinology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Zhao Shuangxia
Department of Molecular Diagnostic, Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Zhu Hui
Department of Endocrinology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Han Bing
Department of Endocrinology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Xu Yue
Department of Endocrinology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Yao Haijun
Department of Urology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Liu Yang
Department of Plastic Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Chen Yan
Department of Obstetrics-Gynecology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Cheng Kaixiang
Department of Plastic Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Song Huaidong
Department of Molecular Diagnostic, Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
Qiao Jie
Department of Endocrinology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
