Exploration of the pathogenesis for a SRY-negative male with 46,XX disorder of sex development.
10.3760/cma.j.cn511374-20191029-00548
- VernacularTitle:SRY阴性46，XX性别发育异常致病原因分析
- Author:
Ailing LIU
1
;
Lanxue ZHANG
;
Hongyan XU
;
Baoqiang CHONG
;
Xiaxia LIU
;
Lin LI
Author Information
1. Department of Genetics Testing, Linyi People's Hospital, Linyi, Shandong 276003, China. lilinxy1996@sina.com.
- Publication Type:Journal Article
- MeSH:
Disorders of Sex Development/genetics*;
Female;
Humans;
Male;
Mutation/genetics*;
Regulatory Sequences, Nucleic Acid/genetics*;
Sex-Determining Region Y Protein/genetics*;
Testis;
Whole Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2020;37(12):1403-1406
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the pathogenesis for a SRY-negative male with 46,XX disorder of sex development (DSD).
METHODS:Peripheral blood samples of the patient and his family members were subjected to chromosomal karyotyping, routine PCR, real-time fluorescence quantitative PCR, whole exome sequencing and whole genome sequencing. The data was analyzed with NextGENe software.
RESULTS:Both the proband and his brother presented a 46,XX karyotype with negative SRY gene, while their father presented normal phenotype and karyotype with positive SRY gene. No pathogenic variant associated with sex development was detected by whole exome sequencing, while a 243 kb duplication was detected by whole genome sequencing in the 5' upstream region of the SOX9 gene in the proband, his brother and father. The same duplication was not found in his sister and mother.
CONCLUSION:The 243 kb duplication at the 5' upstream of the SOX9 gene may predispose to the 46,XX DSD in this family. It is speculated that there exist an unknown core regulatory element in the upstream of the SOX9, and its duplication may trigger expression of SOX9 and initiate testicular differentiation in the absence of SRY gene.
