Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development.

Hu Lin; Hao Yang; Jun Fen FU; Jin Na Yuan; Ke Huang; Wei WU; Guan Ping Dong; Hong Juan Tian; De Hua WU; Da Xing Tang; Ding Wen WU; Li Ying Sun; Ya Lei PI; Li Jun Liu; Li Ping Shi; Wei GU; Lu Gang Huang; Yi Hua Wang; Lin Qi Chen; Hong Ying LI; Yang YU; Hai Yan Wei; Xin Ran Cheng; Xiao Ou Shan; Yu Liu; Xu XU; Shu Liu; Xiao Ping Luo; Yan Feng Xiao; Yu Yang; Gui Mei LI; Mei Feng; Xiu Qi MA; Dao Xiang Pan; Jia Yan Tang; Rui Min Chen; Mireguli Maimaiti; De Yun Liu; Xin Hai Cui; Zhe SU; Zhi Qiao Dong; Li Zou; Yan Ling Liu; Jin WU; Kun Xia LI; Yuan LI

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Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development.

VernacularTitle:中国性发育异常患儿临床表型与基因型分析
Author: Hu LIN ¹ ; Hao YANG ² ; Jun Fen FU ¹ ; Jin Na YUAN ¹ ; Ke HUANG ¹ ; Wei WU ¹ ; Guan Ping DONG ¹ ; Hong Juan TIAN ² ; De Hua WU ² ; Da Xing TANG ² ; Ding Wen WU ³ ; Li Ying SUN ⁴ ; Ya Lei PI ⁵ ; Li Jun LIU ⁶ ; Li Ping SHI ⁷ ; Wei GU ⁸ ; Lu Gang HUANG ⁹ ; Yi Hua WANG ¹⁰ ; Lin Qi CHEN ¹¹ ; Hong Ying LI ¹² ; Yang YU ¹³ ; Hai Yan WEI ¹⁴ ; Xin Ran CHENG ¹⁵ ; Xiao Ou SHAN ¹⁶ ; Yu LIU ¹⁷ ; Xu XU ¹⁸ ; Shu LIU ¹⁹ ; Xiao Ping LUO ²⁰ ; Yan Feng XIAO ²¹ ; Yu YANG ²² ; Gui Mei LI ²³ ; Mei FENG ²⁴ ; Xiu Qi MA ²⁵ ; Dao Xiang PAN ²⁶ ; Jia Yan TANG ²⁷ ; Rui Min CHEN ²⁸ ; Mireguli MAIMAITI ²⁹ ; De Yun LIU ³⁰ ; Xin Hai CUI ³¹ ; Zhe SU ³² ; Zhi Qiao DONG ³³ ; Li ZOU ³⁴ ; Yan Ling LIU ³⁵ ; Jin WU ³⁶ ; Kun Xia LI ³⁷ ; Yuan LI ³⁸
Author Information

1. Department of Endocrinology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
2. Department of Urology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
3. Department of Genetics and Metabolism, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
4. Department of Children's Gynecology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
5. Department of Pediatrics, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
6. Department of Metabolism, Hebei Children's Hospital, Shijiazhuang 050031, China.
7. Department of Urology, Hebei Children's Hospital, Shijiazhuang 050031, China.
8. Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China.
9. Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
10. Department of Endocrinology and Metabolism, Genetics, Xi'an Children's Hospital, Xi'an 710003, China.
11. Department of Endocrinology and Metabolism, Genetics, Children's Hospital of Soochow University, Suzhou 215300, China.
12. Department of Endocrinology, Jinan Children's Hospital, Jinan 250000, China.
13. Department of Pediatric Surgery, Jinan Children's Hospital, Jinan 250000, China.
14. Department of Endocrinology and Metabolism, Genetics, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China.
15. Department of Endocrinology and Metabolism, Genetics, Chengdu Women's and Children's Central Hospital, Chengdu 611731, China.
16. Department of Pediatric Endocrinology and Metabolism, Genetics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
17. Department of Endocrinology and Metabolism, Genetics, Maternal and Child Health-Care Hospital in Guiyang, Guiyang 550003, China.
18. Department of Endocrinology, Wuxi Children's Hospital, Wuxi 214023, China.
19. Department of Endocrinology and Metabolism, Genetics, Guangdong Women and Children Hospital, Guangzhou 511442, China.
20. Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
21. Department of Pediatrics, the Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710004, China.
22. Department of Endocrinology and Metabolism, Genetics, Jiangxi Provicial Children's Hospital, Nanchang 330006, China.
23. Department of Pediatric Endocrine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250014, China.
24. Department of Endocrinology and Metabolism, Genetics, Children's Hospital of Shanxi Province, Taiyuan 030013, China.
25. Department of Pediatrics, Guizhou Provincial People's Hospital, Guiyang 550002, China.
26. Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
27. Department of Pediatrics, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan 528403, China.
28. Department of Endocrinology, Fuzhou Children's Hospital of Fujian Medical University, Fuzhou 350005, China.
29. Department of Pediatrics, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
30. Department of Pediatrics, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
31. Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
32. Department of Endocrinology, Shenzhen Children's Hospital, Shenzhen 518023, China.
33. Department of Pediatrics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou 450009, China.
34. Department of Child Health Care, Linyi Peoples Hospital, Linyi 276000, China.
35. Department of Pediatrics, the Second Affiliated Hospital of Nanchang University, Nangchang 330006, China.
36. Department of Pediatrics Endocrinology and Metabolism, Genetics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
37. Department of Pediatrics, the Affiliated Yantai Yuhuangding Hospital, Yantai 264000, China.
38. Department of Pediatrics, First People's Hospital of Yunnan Province, Kunming 650032, China.
Publication Type:Journal Article
MeSH: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*; Child; China/epidemiology*; Cryptorchidism/genetics*; Disorders of Sex Development/genetics*; Female; Genital Diseases, Male; Genotype; Humans; Hypospadias/genetics*; Male; Membrane Proteins/genetics*; Penis/abnormalities*; Phenotype; Retrospective Studies; Steroid 21-Hydroxylase/genetics*
From: Chinese Journal of Pediatrics 2022;60(5):435-441
CountryChina
Language:Chinese
Abstract: Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.