PMP22-related disease: A novel splice site acceptor variant and intrafamilial phenotype variability.
Gene dose effect
Overlapped pathophysiology
PMP22 protein with in-frame deletion
PMP22-related disease
Splice site acceptor variant
Journal
Neuromuscular disorders : NMD
ISSN: 1873-2364
Titre abrégé: Neuromuscul Disord
Pays: England
ID NLM: 9111470
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
12
12
2018
accepted:
20
03
2019
pubmed:
28
5
2019
medline:
4
7
2020
entrez:
25
5
2019
Statut:
ppublish
Résumé
PMP22 is the most frequent mutated gene in Charcot-Marie-Tooth disease (CMT) type 1A. Another phenotype, hereditary neuropathy with pressure palsies (HNPP), could be caused by PMP22 mutations. PMP22 encodes a peripheral myelin protein with molecular weight 22-kDa. Various pathomechanisms have been postulated in PMP22-related disease, including dysfunction due to missense mutations, and alteration of a gene dose due to duplication/deletion mutations. We identified a novel PMP22 splice site acceptor variant, c.179-1G>A, in a patient with adult-onset chronic generalized polyneuropathy and two asymptomatic family members. Pathophysiological features of the members mainly overlapped with those reported in HNPP, but broad intrafamilial clinical variations were observed. PMP22 transcripts lacking of exon 4 were produced by the variant, presumably leading to in-frame deletion of 47 amino acids. The variant was also shown to exert effect on dosage of PMP22 mRNA. The complex molecular pathology would lead to the unique clinical and pathophysiological conditions.
Identifiants
pubmed: 31122831
pii: S0960-8966(18)31360-9
doi: 10.1016/j.nmd.2019.03.010
pii:
doi:
Substances chimiques
Myelin Proteins
0
PMP22 protein, human
0
RNA Splice Sites
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
422-426Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.