PDF
Full
Outline
Objective To elucidate the molecular genetic etiology of patients with disorders of sex development (DSD) using whole exome sequencing (WES), thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities. Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021, with an additional family study for one proband. Genomic DNA was extracted from patients for WES analysis. Single nucleotide polymorphism (SNP) and insertions/deletion (InDel) tests were identified using SAMtools software in conjunction with established SNP and InDel databases. Copy number variations (CNVs) at the exon level were detected using ExomeDepth, while the potential pathogenicity of mutations was predicted with PolyPhen-2, Mutation taster and PyMol software, with Sanger sequencing employed for confirmation. Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD. Among the 46,XX DSD patients, the SRY gene was detected in 14 patients. In the remaining 8 patients and a proband's families, single nucleotide site variations (SNVs) of NR5A1, PROKR2 and ANOS1 genes were identified in 2 patients, and CNVs in CYP21A2 gene were found in 4 patients. The pathogenicity of CYP21A2 EX1 Dup has been previously reported, while the remaining 3 CNVs were of uncertain significance, and no DSD-related mutations were detected in 2 patients. In the WES analysis of 46,XY DSD patients, 10 pathogenic or likely pathogenic SNVs across 5 genes (SRY, AR, SRD5A2, CYP17A1, and NR5A1) were identified in 14 patients. Additionally, 5 likely pathogenic CNVs involving the CYP21A2, AKR1C2, CBX2, and NR5A1 genes were detected in 5 patients, comprising 3 deletions and 2 duplications. Novel SNVs in NR5A1 (c.722G>T, c.48C>G) and ANOS1 c.564A>T were identified, with no prior reports in relevant databases. The pathogenicity of CYP21A2 EX1 Dup is documented in related databases, while the remaining CNVs have not been previously reported. Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD, broadened the spectrum of known DSD-related gene mutations, and deepened our comprehension of DSD pathogenesis, offering valuable support for genetic counseling.
PDF
181
78
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
关闭全屏
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
