File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: PMCA4 (ATP2B4) Mutation in Familial Spastic Paraplegia

TitlePMCA4 (ATP2B4) Mutation in Familial Spastic Paraplegia
Authors
Issue Date2014
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2014, v. 9 n. 8, article no. e104790 How to Cite?
AbstractFamilial 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.
Persistent Identifierhttp://hdl.handle.net/10722/203367
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLi, M-
dc.contributor.authorHo, PWL-
dc.contributor.authorPang, SYY-
dc.contributor.authorTse, ZHM-
dc.contributor.authorKung, MHW-
dc.contributor.authorSham, PC-
dc.contributor.authorHo, SL-
dc.date.accessioned2014-09-19T14:14:00Z-
dc.date.available2014-09-19T14:14:00Z-
dc.date.issued2014-
dc.identifier.citationPLoS One, 2014, v. 9 n. 8, article no. e104790-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/203367-
dc.description.abstractFamilial 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.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titlePMCA4 (ATP2B4) Mutation in Familial Spastic Paraplegia-
dc.typeArticle-
dc.identifier.emailLi, M: mxli@hku.hk-
dc.identifier.emailHo, PWL: hwl2002@hku.hk-
dc.identifier.emailPang, SYY: pang.shirley@gmail.com-
dc.identifier.emailTse, ZHM: zerotse@hku.hk-
dc.identifier.emailKung, MHW: mhwkung@HKUCC.hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailHo, SL: slho@hku.hk, slho@hkucc.hku.hk-
dc.identifier.authorityLi, M=rp01722en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0104790-
dc.identifier.pmid25119969-
dc.identifier.pmcidPMC4132067-
dc.identifier.hkuros238969-
dc.identifier.hkuros235455-
dc.identifier.volume9-
dc.identifier.issue8-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats