Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies
The white matter disease spectrum is associated with many genetic diseases, including AARS2, CADASIL, ALD, and others. In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.01321/full |
| _version_ | 1828452514728509440 |
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| author | Xingao Wang Xingao Wang Qun Wang Qun Wang Qun Wang Qun Wang Hefei Tang Hefei Tang Bin Chen Bin Chen Xiang Dong Songtao Niu Songtao Niu Shaowu Li Yuzhi Shi Yuzhi Shi Wei Shan Wei Shan Wei Shan Wei Shan Zaiqiang Zhang Zaiqiang Zhang |
| author_facet | Xingao Wang Xingao Wang Qun Wang Qun Wang Qun Wang Qun Wang Hefei Tang Hefei Tang Bin Chen Bin Chen Xiang Dong Songtao Niu Songtao Niu Shaowu Li Yuzhi Shi Yuzhi Shi Wei Shan Wei Shan Wei Shan Wei Shan Zaiqiang Zhang Zaiqiang Zhang |
| author_sort | Xingao Wang |
| collection | DOAJ |
| description | The white matter disease spectrum is associated with many genetic diseases, including AARS2, CADASIL, ALD, and others. In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white matter disease were analyzed by whole-exome sequencing. Variants were prioritized according to their rarity and pathogenic variants in genes already known to be associated with leukodystrophies and were confirmed by Sanger sequencing using standard protocols. We identified 5 rare variants (c.452T>C chr6:44279256 p.M151T, c.1871G>A chr6:44272054 p.W624X, c.802A>G chr6:44278128 p.M268V, c.1703-1704del chr6:-44272430-44272431 p.Q568fs, and c.179C>A chr6-44280882 p.P60H) with varying expression in 4 independent Chinese families with leukodystrophy. These single nucleotide variants (SNVs), or deletion mutations, each induced a frameshift, causing a missense mutation in alanyl-tRNA synthetase 2. These findings suggested that all mutations might contribute to the development of leukodystrophy in the examined family members. Combined with previous findings, our data confirmed that the novel mutations are located in leukodystrophy-related risk genes. We also summarized all the alanyl-tRNA synthetase 2 mutations related to the onset of leukodystrophies in adults. |
| first_indexed | 2024-12-10T23:53:02Z |
| format | Article |
| id | doaj.art-59c33664712c4510834cc282c436ceea |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-10T23:53:02Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-59c33664712c4510834cc282c436ceea2022-12-22T01:28:40ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-12-011010.3389/fneur.2019.01321492158Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in LeukodystrophiesXingao Wang0Xingao Wang1Qun Wang2Qun Wang3Qun Wang4Qun Wang5Hefei Tang6Hefei Tang7Bin Chen8Bin Chen9Xiang Dong10Songtao Niu11Songtao Niu12Shaowu Li13Yuzhi Shi14Yuzhi Shi15Wei Shan16Wei Shan17Wei Shan18Wei Shan19Zaiqiang Zhang20Zaiqiang Zhang21Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurology, Epilepsy Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaBeijing Institute of Neurosurgery, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaDepartment of Neurology, Epilepsy Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaThe white matter disease spectrum is associated with many genetic diseases, including AARS2, CADASIL, ALD, and others. In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white matter disease were analyzed by whole-exome sequencing. Variants were prioritized according to their rarity and pathogenic variants in genes already known to be associated with leukodystrophies and were confirmed by Sanger sequencing using standard protocols. We identified 5 rare variants (c.452T>C chr6:44279256 p.M151T, c.1871G>A chr6:44272054 p.W624X, c.802A>G chr6:44278128 p.M268V, c.1703-1704del chr6:-44272430-44272431 p.Q568fs, and c.179C>A chr6-44280882 p.P60H) with varying expression in 4 independent Chinese families with leukodystrophy. These single nucleotide variants (SNVs), or deletion mutations, each induced a frameshift, causing a missense mutation in alanyl-tRNA synthetase 2. These findings suggested that all mutations might contribute to the development of leukodystrophy in the examined family members. Combined with previous findings, our data confirmed that the novel mutations are located in leukodystrophy-related risk genes. We also summarized all the alanyl-tRNA synthetase 2 mutations related to the onset of leukodystrophies in adults.https://www.frontiersin.org/article/10.3389/fneur.2019.01321/fullleukodystrophiesAARS2pathogenic variantswhite mattermutation |
| spellingShingle | Xingao Wang Xingao Wang Qun Wang Qun Wang Qun Wang Qun Wang Hefei Tang Hefei Tang Bin Chen Bin Chen Xiang Dong Songtao Niu Songtao Niu Shaowu Li Yuzhi Shi Yuzhi Shi Wei Shan Wei Shan Wei Shan Wei Shan Zaiqiang Zhang Zaiqiang Zhang Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies Frontiers in Neurology leukodystrophies AARS2 pathogenic variants white matter mutation |
| title | Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies |
| title_full | Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies |
| title_fullStr | Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies |
| title_full_unstemmed | Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies |
| title_short | Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies |
| title_sort | novel alanyl trna synthetase 2 pathogenic variants in leukodystrophies |
| topic | leukodystrophies AARS2 pathogenic variants white matter mutation |
| url | https://www.frontiersin.org/article/10.3389/fneur.2019.01321/full |
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