Clinical characteristics and genetic analysis of four cases with disorder of sex development
10.3760/cma.j.cn511374-20250825-00510
- VernacularTitle:性发育异常患者4例的临床特征及遗传学分析
- Author:
Xiuyan WANG
1
;
Fanrong MENG
1
;
Yunfang SHI
1
;
Duan JU
1
;
Xinghong ZHOU
1
;
Haiwei DONG
1
;
Xiaozhou LI
1
Author Information
1. 天津医科大学总医院妇产科，天津市女性生殖健康与优生重点实验室，天津 300052
- Publication Type:Journal Article
- Keywords:
Disorder of sex development;
Chromosomal karyotyping analysis;
Low-depth whole genome sequencing;
Fluorescence in situ hybridization;
Whole exo
- From:
Chinese Journal of Medical Genetics
2025;42(9):1089-1095
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD).Methods:Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y ( SRY) gene and azoospermia factor ( AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). Results:Case 1 had a karyotype of 45, X[22]/46, XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+ ), AZFb+ c (-). Case 2 had a karyotype of 45, X[12]/46, X, del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46, XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+ ) and AZFa+ b+ c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46, XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+ ) and AZFa+ b+ c (+ ), and WES revealed a c. 1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+ PP1+ PM2_Supporting). Conclusion:The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.
