46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China
The present study describes the first prenatally diagnosed 46,XX testicular disorders of sex development (46,XX testicular DSD) case with DMD gene mutation by integrated analyses in a Chinese pedigree. Chromosome karyotype G-banding analysis of the proband showed a 46,XX karyotype, but B-ultrasound...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-02-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.01350/full |
| _version_ | 1831671087269675008 |
|---|---|
| author | Jianlian Deng Jianlian Deng Haoqing Zhang Caiyun Li Hui Huang Saijun Liu Huanming Yang Huanming Yang Kaili Xie Qiong Wang Dongzhu Lei Jing Wu |
| author_facet | Jianlian Deng Jianlian Deng Haoqing Zhang Caiyun Li Hui Huang Saijun Liu Huanming Yang Huanming Yang Kaili Xie Qiong Wang Dongzhu Lei Jing Wu |
| author_sort | Jianlian Deng |
| collection | DOAJ |
| description | The present study describes the first prenatally diagnosed 46,XX testicular disorders of sex development (46,XX testicular DSD) case with DMD gene mutation by integrated analyses in a Chinese pedigree. Chromosome karyotype G-banding analysis of the proband showed a 46,XX karyotype, but B-ultrasound analysis demonstrated the existence of scrotum, testis and penis which inferred a male sexual differentiation. Aneuploidy and copy number variation (CNV) detection by low-coverage single-end whole genome sequencing (WGS) revealed a de novo SRY (sex-determining region Y) gene positive fragment of 224.34 kb length (chrY:2,649,472-2,873,810) which explained the gonadal/genital-chromosomal inconsistency in the proband. Additionally, targeted-region-capture-based DMD gene sequencing and Sanger verification confirmed a widely reported pathogenic heterozygous nonsense mutation (NM_004006, c.9100C>T, p.Arg3034Ter) in the dystrophin-coding gene named DMD. This study emphasizes that integrated analyses of the imaging results, cytogenetics, and molecular features can play an important role in prenatal diagnosis. It requires the combination of more detection techniques with higher resolution than karyotyping to determine the genetic and biological sex of fetuses in prenatal diagnosis. To conclusively determine both the biological and genetic sex of the fetus at the time of prenatal diagnosis particularly in cases that involve X-linked conditions is of vital importance, which would crucially influence the decision-making regarding abortions. This study will help in prenatal diagnosis of DMD in future, also providing a new perspective that enables the genetic diagnosis of sex reversal in pregnancy. Moreover, genetic counseling/analysis for early diagnosis and pre-symptom interventions are warranted. |
| first_indexed | 2024-12-19T23:29:07Z |
| format | Article |
| id | doaj.art-aac9e5436c4b4ec3a39c77b3d0369155 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T23:29:07Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-aac9e5436c4b4ec3a39c77b3d03691552022-12-21T20:01:46ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-02-011010.3389/fgene.2019.0135049394646,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in ChinaJianlian Deng0Jianlian Deng1Haoqing Zhang2Caiyun Li3Hui Huang4Saijun Liu5Huanming Yang6Huanming Yang7Kaili Xie8Qiong Wang9Dongzhu Lei10Jing Wu11School of Future Technology, University of Chinese Academy of Sciences, Beijing, ChinaBGI-Shenzhen, Shenzhen, ChinaCenter of Prenatal Diagnosis, Chenzhou No.1 People’s Hospital, Hunan, ChinaCenter of Prenatal Diagnosis, Chenzhou No.1 People’s Hospital, Hunan, ChinaBGI Genomics, BGI-Shenzhen, Shenzhen, ChinaBGI Genomics, BGI-Shenzhen, Shenzhen, ChinaBGI-Shenzhen, Shenzhen, ChinaJames D. Watson Institute of Genome Sciences, Hangzhou, ChinaDivision of Obstetrics，Zhuzhou Central Hospital, Hunan, ChinaGenetic Eugenics Division, The Maternal and Child Health Hospital of Changde City, Hunan, ChinaCenter of Prenatal Diagnosis, Chenzhou No.1 People’s Hospital, Hunan, ChinaBGI Genomics, BGI-Shenzhen, Shenzhen, ChinaThe present study describes the first prenatally diagnosed 46,XX testicular disorders of sex development (46,XX testicular DSD) case with DMD gene mutation by integrated analyses in a Chinese pedigree. Chromosome karyotype G-banding analysis of the proband showed a 46,XX karyotype, but B-ultrasound analysis demonstrated the existence of scrotum, testis and penis which inferred a male sexual differentiation. Aneuploidy and copy number variation (CNV) detection by low-coverage single-end whole genome sequencing (WGS) revealed a de novo SRY (sex-determining region Y) gene positive fragment of 224.34 kb length (chrY:2,649,472-2,873,810) which explained the gonadal/genital-chromosomal inconsistency in the proband. Additionally, targeted-region-capture-based DMD gene sequencing and Sanger verification confirmed a widely reported pathogenic heterozygous nonsense mutation (NM_004006, c.9100C>T, p.Arg3034Ter) in the dystrophin-coding gene named DMD. This study emphasizes that integrated analyses of the imaging results, cytogenetics, and molecular features can play an important role in prenatal diagnosis. It requires the combination of more detection techniques with higher resolution than karyotyping to determine the genetic and biological sex of fetuses in prenatal diagnosis. To conclusively determine both the biological and genetic sex of the fetus at the time of prenatal diagnosis particularly in cases that involve X-linked conditions is of vital importance, which would crucially influence the decision-making regarding abortions. This study will help in prenatal diagnosis of DMD in future, also providing a new perspective that enables the genetic diagnosis of sex reversal in pregnancy. Moreover, genetic counseling/analysis for early diagnosis and pre-symptom interventions are warranted.https://www.frontiersin.org/article/10.3389/fgene.2019.01350/fullintegrated analyses46,XX testicular DSDDuchenne muscular dystrophyprenatalgenetic counseling |
| spellingShingle | Jianlian Deng Jianlian Deng Haoqing Zhang Caiyun Li Hui Huang Saijun Liu Huanming Yang Huanming Yang Kaili Xie Qiong Wang Dongzhu Lei Jing Wu 46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China Frontiers in Genetics integrated analyses 46,XX testicular DSD Duchenne muscular dystrophy prenatal genetic counseling |
| title | 46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China |
| title_full | 46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China |
| title_fullStr | 46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China |
| title_full_unstemmed | 46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China |
| title_short | 46,XX Testicular Disorders of Sex Development With DMD Gene Mutation: First Case Report Identified Prenatally by Integrated Analyses in China |
| title_sort | 46 xx testicular disorders of sex development with dmd gene mutation first case report identified prenatally by integrated analyses in china |
| topic | integrated analyses 46,XX testicular DSD Duchenne muscular dystrophy prenatal genetic counseling |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.01350/full |
| work_keys_str_mv | AT jianliandeng 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT jianliandeng 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT haoqingzhang 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT caiyunli 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT huihuang 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT saijunliu 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT huanmingyang 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT huanmingyang 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT kailixie 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT qiongwang 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT dongzhulei 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina AT jingwu 46xxtesticulardisordersofsexdevelopmentwithdmdgenemutationfirstcasereportidentifiedprenatallybyintegratedanalysesinchina |