Identification of CHIP as a Novel Causative Gene for Autosomal Recessive Cerebellar Ataxia
| العنوان: | Identification of CHIP as a Novel Causative Gene for Autosomal Recessive Cerebellar Ataxia |
|---|---|
| المؤلفون: | Xiao Jingjing, Zhengmao Hu, Zhuohua Zhang, Juan Du, Kun Xia, Miao He, Yacen Hu, Yuting Shi, Hong Jiang, Li Shen, Jia-Da Li, Jifeng Guo, Qian Pan, Yafang Zhou, Junling Wang, Qian Ya Xu, Jun Wang, Haigang Ren, Nan Li, Fu-feng Zhang, Ying Zhou, Weiqian Yan, Guanghui Wang, Zheng Su, Wen-Juan Guan, Beisha Tang, Jianguo Zhang, Mei-zhi Dai |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 12, p e81884 (2013) Shi, Y, Wang, J, Li, J-D, Ren, H, Guan, W, He, M, Yan, W, Zhou, Y, Hu, Z, Zhang, J, Xiao, J, Su, Z, Dai, M, Wang, J, Jiang, H, Guo, J, Zhou, Y, Zhang, F, Li, N, Du, J, Xu, Q, Hu, Y, Pan, Q, Shen, L, Wang, G, Xia, K, Zhang, Z & Tang, B 2013, ' Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia ', P L o S One, vol. 8, no. 12, e81884 . https://doi.org/10.1371/journal.pone.0081884Test |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, Cerebellum, Ataxia, Cerebellar Ataxia, Genetic Linkage, Ubiquitin-Protein Ligases, Molecular Sequence Data, lcsh:Medicine, Biology, Compound heterozygosity, Mice, Young Adult, symbols.namesake, Genetic linkage, medicine, Animals, Humans, Exome, Amino Acid Sequence, lcsh:Science, Genetics, Sanger sequencing, Multidisciplinary, Cerebellar ataxia, Genetic heterogeneity, lcsh:R, Brain, Autosomal recessive cerebellar ataxia, medicine.disease, Molecular biology, Pedigree, Protein Transport, HEK293 Cells, medicine.anatomical_structure, nervous system, Mutation, symbols, lcsh:Q, Female, medicine.symptom, Research Article |
| الوصف: | Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia. |
| وصف الملف: | application/pdf |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::15f522c9e5779b72dbbbb10909a105fdTest https://doi.org/10.1371/journal.pone.0081884Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....15f522c9e5779b72dbbbb10909a105fd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|