PMCA4 (ATP2B4) mutation in familial spastic paraplegia.
PMCA4 (ATP2B4) mutation in familial spastic paraplegia.
复制标题
DOI：
10.1371/journal.pone.0104790
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ho SL
中科院分区：
文献类型：
--
作者：
Li M;Ho PW;Pang SY;Tse ZH;Kung MH;Sham PC;Ho SL
Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. In this study, we identified a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger sequencing. This mutation co-segregated with the phenotype in the six family members studied and is predicted to be pathogenic when multiple deleteriousness predictions were combined. This novel R268Q mutation was not present in over 7,000 subjects in public databases, and over 1,000 Han Chinese in our database. Prediction of potential functional consequence of R268Q mutation on PMCA4 by computational modeling revealed that this mutation is located in protein aggregation-prone segment susceptible to protein misfolding. Analysis for thermodynamic protein stability indicated that this mutation destabilizes the PMCA4 protein structure with higher folding free energy. As PMCA4 functions to maintain neuronal calcium homeostasis, our result showed that calcium dysregulation may be associated with the pathogenesis of FSP.
登录
查看更多内容
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
13.9
作者：
Blackstone C
通讯作者：
Blackstone C
影响因子：
3.9
作者：
Bettencourt, Conceicao;Quintans, Beatriz;Sobrido, Maria-Jesus
通讯作者：
Sobrido, Maria-Jesus
影响因子：
2.7
作者：
Strehler, Emanuel E.
通讯作者：
Strehler, Emanuel E.
影响因子：
14.9
作者：
Zemla, A
通讯作者：
Zemla, A