Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes
Uniparental disomy (UPD) refers to as both homologous chromosomes inherited from only one parent without identical copies from the other parent. Studies on clinical phenotypes in UPDs are usually focused on the documented UPD 6, 7, 11, 14, 15, and 20, which directly lead to imprinting disorders. Thi...
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| Format: | Article |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1232059/full |
| _version_ | 1797666557709516800 |
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| author | Qi Chen Yunpeng Chen Lin Shi Ying Tao Xiaoguang Li Xiaolan Zhu Yan Yang Wenlin Xu |
| author_facet | Qi Chen Yunpeng Chen Lin Shi Ying Tao Xiaoguang Li Xiaolan Zhu Yan Yang Wenlin Xu |
| author_sort | Qi Chen |
| collection | DOAJ |
| description | Uniparental disomy (UPD) refers to as both homologous chromosomes inherited from only one parent without identical copies from the other parent. Studies on clinical phenotypes in UPDs are usually focused on the documented UPD 6, 7, 11, 14, 15, and 20, which directly lead to imprinting disorders. This study describes clinical phenotypes and genetic findings of three patients with UPD 2, 9, and 14, respectively. Chromosomal microarray (CMA), UPDtool, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and whole-exome sequencing (WES) analysis were performed to characterize the genetic etiology. The CMA revealed a homozygous region involving the whole chromosome 2 and 9, a partial region of homozygosity in chromosome 14. UPD-tool revealed a paternal origin of the UPD2. MS-MLPA showed hypomethylation of imprinting gene MEG3 from maternal origin in the UPD14 case. In addition, UPD14 case displayed complex symptoms including growth failure, hypotonia and acute respiratory distress syndrome (ARDS), accompanied by several gene mutations with heterozygous genotype by WES analysis. Furthermore, we reviewed the documented UPDs and summarized the clinical characteristics and prognosis. This study highlighted the importance to confirm the diagnosis and origin of UPD using genetic testing. Therefore, it is suggested that expanding of the detailed phenotypes and genotypes provide effective guidance for molecule testing and genetic counseling, and promote further biological investigation to the underlying mechanisms of imprinted disorders and accompanied copy number variations. |
| first_indexed | 2024-03-11T20:01:08Z |
| format | Article |
| id | doaj.art-183f217200ab4ab99e7e4ab534a1b9de |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T20:01:08Z |
| publishDate | 2023-10-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-183f217200ab4ab99e7e4ab534a1b9de2023-10-04T08:28:00ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-10-011410.3389/fgene.2023.12320591232059Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomesQi Chen0Yunpeng Chen1Lin Shi2Ying Tao3Xiaoguang Li4Xiaolan Zhu5Yan Yang6Wenlin XuGenetic and Prenatal Diagnosis Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaGenetic and Prenatal Diagnosis Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Ultrasound, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaGenetic and Prenatal Diagnosis Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaGenetic and Prenatal Diagnosis Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaReproductive Medicine Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaGenetic and Prenatal Diagnosis Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaUniparental disomy (UPD) refers to as both homologous chromosomes inherited from only one parent without identical copies from the other parent. Studies on clinical phenotypes in UPDs are usually focused on the documented UPD 6, 7, 11, 14, 15, and 20, which directly lead to imprinting disorders. This study describes clinical phenotypes and genetic findings of three patients with UPD 2, 9, and 14, respectively. Chromosomal microarray (CMA), UPDtool, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and whole-exome sequencing (WES) analysis were performed to characterize the genetic etiology. The CMA revealed a homozygous region involving the whole chromosome 2 and 9, a partial region of homozygosity in chromosome 14. UPD-tool revealed a paternal origin of the UPD2. MS-MLPA showed hypomethylation of imprinting gene MEG3 from maternal origin in the UPD14 case. In addition, UPD14 case displayed complex symptoms including growth failure, hypotonia and acute respiratory distress syndrome (ARDS), accompanied by several gene mutations with heterozygous genotype by WES analysis. Furthermore, we reviewed the documented UPDs and summarized the clinical characteristics and prognosis. This study highlighted the importance to confirm the diagnosis and origin of UPD using genetic testing. Therefore, it is suggested that expanding of the detailed phenotypes and genotypes provide effective guidance for molecule testing and genetic counseling, and promote further biological investigation to the underlying mechanisms of imprinted disorders and accompanied copy number variations.https://www.frontiersin.org/articles/10.3389/fgene.2023.1232059/fulluniparental disomychromosmal microarray analysiswhole exome sequencingchromosome aberrationphenotype |
| spellingShingle | Qi Chen Yunpeng Chen Lin Shi Ying Tao Xiaoguang Li Xiaolan Zhu Yan Yang Wenlin Xu Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes Frontiers in Genetics uniparental disomy chromosmal microarray analysis whole exome sequencing chromosome aberration phenotype |
| title | Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes |
| title_full | Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes |
| title_fullStr | Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes |
| title_full_unstemmed | Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes |
| title_short | Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes |
| title_sort | uniparental disomy expanding the clinical and molecular phenotypes of whole chromosomes |
| topic | uniparental disomy chromosmal microarray analysis whole exome sequencing chromosome aberration phenotype |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1232059/full |
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