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Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex
Author(s) -
Natsuga Ken,
Nishie Wataru,
Akiyama Masashi,
Nakamura Hideki,
Shinkuma Satoru,
McMillan James R.,
Nagasaki Akari,
Has Cristina,
Ouchi Takeshi,
Ishiko Akira,
Hirako Yoshiaki,
Owaribe Katsushi,
Sawamura Daisuke,
BrucknerTuderman Leena,
Shimizu Hiroshi
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21189
Subject(s) - plectin , epidermolysis bullosa simplex , biology , epidermolysis bullosa , microbiology and biotechnology , gene isoform , intermediate filament , muscular dystrophy , exon , genetics , gene , cytoskeleton , cell
Plectin is a cytoskeletal linker protein that has a dumbbell‐like structure with a long central rod and N‐ and C‐terminal globular domains. Mutations in the gene encoding plectin ( PLEC1 ) cause two distinct autosomal recessive subtypes of epidermolysis bullosa (EB): EB simplex with muscular dystrophy (EBS‐MD), and EB simplex with pyloric atresia (EBS‐PA). Here, we demonstrate that normal human fibroblasts express two different plectin isoforms including full‐length and rodless forms of plectin. We performed detailed analysis of plectin expression patterns in six EBS‐MD and three EBS‐PA patients. In EBS‐PA, expression of all plectin domains was found to be markedly attenuated or completely lost; in EBS‐MD, the expression of the N‐ and C‐terminal domains of plectin remained detectable, although the expression of rod domains was absent or markedly reduced. Our data suggest that loss of the full‐length plectin isoform with residual expression of the rodless plectin isoform leads to EBS‐MD, and that complete loss or marked attenuation of full‐length and rodless plectin expression underlies the more severe EBS‐PA phenotype. These results also clearly account for the majority of EBS‐MD PLEC1 mutation restriction within the large exon 31 that encodes the plectin rod domain, whereas EBS‐PA PLEC1 mutations are generally outside exon 31. Hum Mutat 30:1–9, 2010. © 2010 Wiley‐Liss, Inc.