PMID- 30314286
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 7
IP  - 10
DP  - 2018 Oct 11
TI  - PLP1 Mutations in Patients with Multiple Sclerosis: Identification of a New 
      Mutation and Potential Pathogenicity of the Mutations.
LID - 10.3390/jcm7100342 [doi]
LID - 342
AB  - PLP1 is located on the X-chromosome and encodes myelin proteolipid protein (PLP), 
      the most abundant protein in central nervous system myelin. Generally, point 
      mutations in PLP1 result in X-linked dysmyelinating disorders, such as 
      Pelizaeus-Merzbacher disease (PMD) or spastic paraplegia type 2 (SPG2). However, 
      several case studies have identified patients with missense point mutations in 
      PLP1 and clinical symptoms and signs compatible with a diagnosis of multiple 
      sclerosis (MS). To investigate if PLP1 mutations occur relatively frequently in 
      MS, we sequenced the coding regions of PLP1 in 22 female MS patients who had 
      developed disease after the age of 40 and in 42 healthy women, and identified a 
      missense mutation in exon 2 of PLP1 resulting in a Leu30Val mutation in the 
      protein in one of the MS patients. mCherry-tagged plasmids containing wild type 
      or mutant PLP1 sequences of PLP, including two known PMD/SPG2-related mutations 
      as positive controls, were constructed and transfected into Cos-7 cells. In 
      comparison with cells transfected with wild type PLP1, all mutations caused 
      significant accumulation of PLP in the endoplasmic reticulum of the cells and 
      induction of the unfolded protein response-a mechanism that leads to apoptosis of 
      cells expressing mutant proteins. Additionally, in silico analysis of the binding 
      of peptides containing the Leu30Val mutation to the human leukocyte antigen (HLA) 
      molecules carried by the patient harboring this mutation suggested that the 
      mutation could produce several novel immunogenic epitopes in this patient. These 
      results support the idea that mutations in myelin-related genes could contribute 
      to the development of MS in a small proportion of patients.
FAU - Cloake, Nancy C
AU  - Cloake NC
AD  - UQ Centre for Clinical Research, the University of Queensland, Brisbane, QLD 
      4029, Australia. Nancy.Cloake@qimrberghofer.edu.au.
FAU - Yan, Jun
AU  - Yan J
AD  - UQ Centre for Clinical Research, the University of Queensland, Brisbane, QLD 
      4029, Australia. j.yan@uq.edu.au.
FAU - Aminian, Atefeh
AU  - Aminian A
AD  - UQ Centre for Clinical Research, the University of Queensland, Brisbane, QLD 
      4029, Australia. atefeh.aminian@yahoo.com.
AD  - School of Medicine, Tehran University of Medical Sciences, Tehran 15119-43943, 
      Iran. atefeh.aminian@yahoo.com.
FAU - Pender, Michael P
AU  - Pender MP
AD  - Faculty of Medicine, the University of Queensland, Brisbane, QLD 4029, Australia. 
      m.pender@uq.edu.au.
AD  - Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, 
      Australia. m.pender@uq.edu.au.
FAU - Greer, Judith M
AU  - Greer JM
AUID- ORCID: 0000-0003-4440-4309
AD  - UQ Centre for Clinical Research, the University of Queensland, Brisbane, QLD 
      4029, Australia. j.greer@uq.edu.au.
LA  - eng
GR  - 10053/Multiple Sclerosis Research Australia/
PT  - Journal Article
DEP - 20181011
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC6210135
OTO - NOTNLM
OT  - epitopes
OT  - multiple sclerosis (MS)
OT  - myelin proteolipid protein (PLP)
OT  - point mutations
OT  - primary progressive MS
OT  - unfolded protein response
OT  - women
COIS- The authors declare no conflict of interest.
EDAT- 2018/10/14 06:00
MHDA- 2018/10/14 06:01
PMCR- 2018/10/11
CRDT- 2018/10/14 06:00
PHST- 2018/09/27 00:00 [received]
PHST- 2018/10/08 00:00 [revised]
PHST- 2018/10/09 00:00 [accepted]
PHST- 2018/10/14 06:00 [entrez]
PHST- 2018/10/14 06:00 [pubmed]
PHST- 2018/10/14 06:01 [medline]
PHST- 2018/10/11 00:00 [pmc-release]
AID - jcm7100342 [pii]
AID - jcm-07-00342 [pii]
AID - 10.3390/jcm7100342 [doi]
PST - epublish
SO  - J Clin Med. 2018 Oct 11;7(10):342. doi: 10.3390/jcm7100342.