Identification of gene mutations in six Chinese patients with maple syrup urine disease
Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.Methods:...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1132364/full |
| _version_ | 1797895491556474880 |
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| author | Lulu Li Xinmei Mao Nan Yang Taoyun Ji Shunan Wang Yulan Ma Haihe Yang Yuting Sang Jinqi Zhao Lifei Gong Yue Tang Yuanyuan Kong |
| author_facet | Lulu Li Xinmei Mao Nan Yang Taoyun Ji Shunan Wang Yulan Ma Haihe Yang Yuting Sang Jinqi Zhao Lifei Gong Yue Tang Yuanyuan Kong |
| author_sort | Lulu Li |
| collection | DOAJ |
| description | Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)—Sanger sequencing technology. Bioinformatics software analyzed the variants’ pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins.Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing’s results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD’s differential diagnosis, early treatment, and prenatal diagnosis. |
| first_indexed | 2024-04-10T07:27:41Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T07:27:41Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-8e733f7333cf43e08399916eb39bebdf2023-02-24T05:07:00ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-02-011410.3389/fgene.2023.11323641132364Identification of gene mutations in six Chinese patients with maple syrup urine diseaseLulu Li0Xinmei Mao1Nan Yang2Taoyun Ji3Shunan Wang4Yulan Ma5Haihe Yang6Yuting Sang7Jinqi Zhao8Lifei Gong9Yue Tang10Yuanyuan Kong11Department of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaPeking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaPeking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaPeking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaPeking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaDepartment of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Healthcare Hospital, Beijing, ChinaBackground: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)—Sanger sequencing technology. Bioinformatics software analyzed the variants’ pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins.Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing’s results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD’s differential diagnosis, early treatment, and prenatal diagnosis.https://www.frontiersin.org/articles/10.3389/fgene.2023.1132364/fullmaple syrup urine diseasehigh-throughput sequencinggene mutationneonatal screeningmetabolic disorders |
| spellingShingle | Lulu Li Xinmei Mao Nan Yang Taoyun Ji Shunan Wang Yulan Ma Haihe Yang Yuting Sang Jinqi Zhao Lifei Gong Yue Tang Yuanyuan Kong Identification of gene mutations in six Chinese patients with maple syrup urine disease Frontiers in Genetics maple syrup urine disease high-throughput sequencing gene mutation neonatal screening metabolic disorders |
| title | Identification of gene mutations in six Chinese patients with maple syrup urine disease |
| title_full | Identification of gene mutations in six Chinese patients with maple syrup urine disease |
| title_fullStr | Identification of gene mutations in six Chinese patients with maple syrup urine disease |
| title_full_unstemmed | Identification of gene mutations in six Chinese patients with maple syrup urine disease |
| title_short | Identification of gene mutations in six Chinese patients with maple syrup urine disease |
| title_sort | identification of gene mutations in six chinese patients with maple syrup urine disease |
| topic | maple syrup urine disease high-throughput sequencing gene mutation neonatal screening metabolic disorders |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1132364/full |
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