Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China
Abstract Background Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chromosome 15q11.2-q13.3 region. Methods 3331 individuals was recruited from June 2013 to Decembe...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Molecular Cytogenetics |
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| Online Access: | http://link.springer.com/article/10.1186/s13039-019-0420-x |
| _version_ | 1818984289930313728 |
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| author | Chang Liu Xiangzhong Zhang Jicheng Wang Yan Zhang Anshi Wang Jian Lu Yanlin Huang Shu Liu Jing Wu Li Du Jie Yang Hongke Ding Ling Liu Xin Zhao Aihua Yin |
| author_facet | Chang Liu Xiangzhong Zhang Jicheng Wang Yan Zhang Anshi Wang Jian Lu Yanlin Huang Shu Liu Jing Wu Li Du Jie Yang Hongke Ding Ling Liu Xin Zhao Aihua Yin |
| author_sort | Chang Liu |
| collection | DOAJ |
| description | Abstract Background Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chromosome 15q11.2-q13.3 region. Methods 3331 individuals was recruited from June 2013 to December 2016 under an institutional review board-approved protocol of informed consent. The methylation-specific PCR was employed as a first-tier screening test. The multiplex-fluorescent-labeled STR linkage analysis was carried out to define the underlying genetic mechanisms. The chromosomal microarray analysis was employed to identify chromosomal breakpoints in confirmed cases, and to detect other chromosomal abnormalities in undiagnosed cases. Genetic counseling and recurrence risk assessment were provided to families with affected individuals. Results The methylation-specific PCR identified 36 PWS suspected patients and 13 AS suspected patients. UBE3A sequence analysis identified another 1 patient with AS. The STR linkage analysis define the underlying genetic mechanisms. Thirty PWS patients were with paternal deletions on chromosome region 15q11-q13, 5 with isodisomic uniparental disomy and 1 with mixed segmental isodisomic/ heterodisomic uniparental disomy of maternal chromosome 15. Twelve AS patients were with maternal deletions, 1 with isodisomic uniparental disomy and 1 with UBE3A gene mutation. The chromosomal microarray analysis identified chromosomal breakpoints in confirmed cases, and detected chromosomal abnormalities in another 4 patients with clinically overlapped features but tested negative for PWS/AS. Genetic counseling was offered to all families with affected individuals. Conclusions Identifying the disorders at early age, establishing the molecular mechanisms, carrying out treatment intervention and close monitoring can significantly improve the prognosis of PWS/AS patients. |
| first_indexed | 2024-12-20T18:16:39Z |
| format | Article |
| id | doaj.art-740f55fe752145d5a2778a23ea48b268 |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-12-20T18:16:39Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cytogenetics |
| spelling | doaj.art-740f55fe752145d5a2778a23ea48b2682022-12-21T19:30:22ZengBMCMolecular Cytogenetics1755-81662019-02-011211910.1186/s13039-019-0420-xGenetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, ChinaChang Liu0Xiangzhong Zhang1Jicheng Wang2Yan Zhang3Anshi Wang4Jian Lu5Yanlin Huang6Shu Liu7Jing Wu8Li Du9Jie Yang10Hongke Ding11Ling Liu12Xin Zhao13Aihua Yin14Medical Genetic Center, Guangdong Women and Children HospitalDepartment of Hematology, The Third Affiliated Hospital of Sun Yat-sen UniversityMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalChildren Inherited Metabolism and Endocrine Department, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalDepartment of Neonatology, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalMedical Genetic Center, Guangdong Women and Children HospitalAbstract Background Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chromosome 15q11.2-q13.3 region. Methods 3331 individuals was recruited from June 2013 to December 2016 under an institutional review board-approved protocol of informed consent. The methylation-specific PCR was employed as a first-tier screening test. The multiplex-fluorescent-labeled STR linkage analysis was carried out to define the underlying genetic mechanisms. The chromosomal microarray analysis was employed to identify chromosomal breakpoints in confirmed cases, and to detect other chromosomal abnormalities in undiagnosed cases. Genetic counseling and recurrence risk assessment were provided to families with affected individuals. Results The methylation-specific PCR identified 36 PWS suspected patients and 13 AS suspected patients. UBE3A sequence analysis identified another 1 patient with AS. The STR linkage analysis define the underlying genetic mechanisms. Thirty PWS patients were with paternal deletions on chromosome region 15q11-q13, 5 with isodisomic uniparental disomy and 1 with mixed segmental isodisomic/ heterodisomic uniparental disomy of maternal chromosome 15. Twelve AS patients were with maternal deletions, 1 with isodisomic uniparental disomy and 1 with UBE3A gene mutation. The chromosomal microarray analysis identified chromosomal breakpoints in confirmed cases, and detected chromosomal abnormalities in another 4 patients with clinically overlapped features but tested negative for PWS/AS. Genetic counseling was offered to all families with affected individuals. Conclusions Identifying the disorders at early age, establishing the molecular mechanisms, carrying out treatment intervention and close monitoring can significantly improve the prognosis of PWS/AS patients.http://link.springer.com/article/10.1186/s13039-019-0420-xPrader-Willi syndromeAngelman syndromeGenetic testingClinical practice |
| spellingShingle | Chang Liu Xiangzhong Zhang Jicheng Wang Yan Zhang Anshi Wang Jian Lu Yanlin Huang Shu Liu Jing Wu Li Du Jie Yang Hongke Ding Ling Liu Xin Zhao Aihua Yin Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China Molecular Cytogenetics Prader-Willi syndrome Angelman syndrome Genetic testing Clinical practice |
| title | Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China |
| title_full | Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China |
| title_fullStr | Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China |
| title_full_unstemmed | Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China |
| title_short | Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China |
| title_sort | genetic testing for prader willi syndrome and angelman syndrome in the clinical practice of guangdong province china |
| topic | Prader-Willi syndrome Angelman syndrome Genetic testing Clinical practice |
| url | http://link.springer.com/article/10.1186/s13039-019-0420-x |
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