Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia.
Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia.
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CHIP 鉴定为常染色体隐性小脑性共济失调的新致病基因
DOI：
10.1371/journal.pone.0081884
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Shi Y;Wang J;Li JD;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
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.
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影响因子：
3.5
作者：
Ding, JQ;Allen, E;Yang, YM
通讯作者：
Yang, YM
影响因子：
4.8
作者：
Jiang, JH;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C
DOI：
10.1016/j.bbrc.2004.10.037
发表时间：
2004-12-03
影响因子：
3.1
作者：
Klucken, J;Shin, Y;McLean, PJ
通讯作者：
McLean, PJ
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
6.1
作者：
Altafaj, X.;Ortiz-Abalia, J.;Fillat, C.
通讯作者：
Fillat, C.