Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.
Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.119 patients with hy...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5815574?pdf=render |
| _version_ | 1819172976078094336 |
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| author | Haoran Ji Dongxiao Li Ye Wu Quanli Zhang Qiang Gu Han Xie Taoyun Ji Huifang Wang Lu Zhao Haijuan Zhao Yanling Yang Hongchun Feng Hui Xiong Jinhua Ji Zhixian Yang Liping Kou Ming Li Xinhua Bao Xingzhi Chang Yuehua Zhang Li Li Huijuan Li Zhengping Niu Xiru Wu Jiangxi Xiao Yuwu Jiang Jingmin Wang |
| author_facet | Haoran Ji Dongxiao Li Ye Wu Quanli Zhang Qiang Gu Han Xie Taoyun Ji Huifang Wang Lu Zhao Haijuan Zhao Yanling Yang Hongchun Feng Hui Xiong Jinhua Ji Zhixian Yang Liping Kou Ming Li Xinhua Bao Xingzhi Chang Yuehua Zhang Li Li Huijuan Li Zhengping Niu Xiru Wu Jiangxi Xiao Yuwu Jiang Jingmin Wang |
| author_sort | Haoran Ji |
| collection | DOAJ |
| description | Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing.Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively.This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders. |
| first_indexed | 2024-12-22T20:15:44Z |
| format | Article |
| id | doaj.art-e7617d905a18452986e1ce20453ec542 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T20:15:44Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e7617d905a18452986e1ce20453ec5422022-12-21T18:13:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01132e018886910.1371/journal.pone.0188869Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.Haoran JiDongxiao LiYe WuQuanli ZhangQiang GuHan XieTaoyun JiHuifang WangLu ZhaoHaijuan ZhaoYanling YangHongchun FengHui XiongJinhua JiZhixian YangLiping KouMing LiXinhua BaoXingzhi ChangYuehua ZhangLi LiHuijuan LiZhengping NiuXiru WuJiangxi XiaoYuwu JiangJingmin WangHypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing.Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively.This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.http://europepmc.org/articles/PMC5815574?pdf=render |
| spellingShingle | Haoran Ji Dongxiao Li Ye Wu Quanli Zhang Qiang Gu Han Xie Taoyun Ji Huifang Wang Lu Zhao Haijuan Zhao Yanling Yang Hongchun Feng Hui Xiong Jinhua Ji Zhixian Yang Liping Kou Ming Li Xinhua Bao Xingzhi Chang Yuehua Zhang Li Li Huijuan Li Zhengping Niu Xiru Wu Jiangxi Xiao Yuwu Jiang Jingmin Wang Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. PLoS ONE |
| title | Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. |
| title_full | Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. |
| title_fullStr | Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. |
| title_full_unstemmed | Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. |
| title_short | Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. |
| title_sort | hypomyelinating disorders in china the clinical and genetic heterogeneity in 119 patients |
| url | http://europepmc.org/articles/PMC5815574?pdf=render |
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