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学科主题: 临床医学
题名:
ATP1A3 Mutations and Genotype-Phenotype Correlation of Alternating Hemiplegia of Childhood in Chinese Patients
作者: Yang, Xiaoling1; Gao, Hua2; Zhang, Jie3; Xu, Xiaojing1; Liu, Xiaoyan1; Wu, Xiru1; Wei, Liping2,3; Zhang, Yuehua1
刊名: PLOS ONE
发表日期: 2014-05-19
DOI: 10.1371/journal.pone.0097274
卷: 9, 期:5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: ONSET DYSTONIA-PARKINSONISM ; DE-NOVO MUTATIONS ; CRYSTAL-STRUCTURE ; SEQUENCING DATA ; GENE MUTATION ; SWISS-MODEL ; WEB SERVER ; MIGRAINE ; IDENTIFICATION ; ENVIRONMENT
英文摘要:

Alternating hemiplegia of childhood (AHC) is a rare and severe neurological disorder. ATP1A3 was recently identified as the causative gene. Here we report the first genetic study in Chinese AHC cohort. We performed whole-exome sequencing on three trios and three unrelated patients, and screened additional 41 typical cases and 100 controls by PCR-Sanger sequencing. ATP1A3 mutations were detected in 95.7% of typical AHC patients. At least 93.3% were de novo. Four late onset, atypical AHC patients were also mutation positive, suggesting the need for testing ATP1A3 mutations in atypical cases. Totally, 13 novel missense mutations (T370N, G706R, L770R, T771N, T771I, S772R, L802P, D805H, M806K, P808L, I810N, L839P and G893R) were identified in our study. By homology modeling of the mutant protein structures and calculation of an extensive list of molecular features, we identified two statistically significant molecular features, solvent accessibility and distance to metal ion, that distinguished disease-associated mutations from neutral variants. A logistic regression classifier achieved 92.9% accuracy by the average of 100 times of five-fold cross validations. Genotype-phenotype correlation analysis showed that patients with epilepsy were more likely to carry E815K mutation. In summary, ATP1A3 is the major pathogenic gene of AHC in Chinese patients; mutations have distinctive molecular features that discriminate them from neutral variants and are correlated with phenotypes.

语种: 英语
所属项目编号: BMU20120308 ; 31025014 ; 2012CB837600 ; 20130001110071
项目资助者: Key Construction Program of the National "985&prime ; &prime ; Project ; National Outstanding Young Investigator Award ; Ministry of Science and Technology of China 973 grant ; Doctoral Fund of Ministry of Education of China
WOS记录号: WOS:000340948600020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57965
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: 1.Natl Inst Biol Sci, Beijing, Peoples R China
2.Peking Univ, Hosp 1, Dept Pediat, Beijing 100871, Peoples R China
3.Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Ctr Bioinformat, Beijing 100871, Peoples R China

Recommended Citation:
Yang, Xiaoling,Gao, Hua,Zhang, Jie,et al. ATP1A3 Mutations and Genotype-Phenotype Correlation of Alternating Hemiplegia of Childhood in Chinese Patients[J]. PLOS ONE,2014,9(5).
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