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Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex
Author(s) -
Natsuga Ken,
Nishie Wataru,
Shinkuma Satoru,
Arita Ken,
Nakamura Hideki,
Ohyama Makiko,
Osaka Hitoshi,
Kambara Takeshi,
Hirako Yoshiaki,
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.21330
Subject(s) - plectin , epidermolysis bullosa simplex , epidermolysis bullosa , muscular dystrophy , biology , proband , exon , genetics , pathology , microbiology and biotechnology , mutation , medicine , intermediate filament , gene , cytoskeleton , cell
Plectin is a cytoskeletal linker protein which has a long central rod and N‐ and C‐terminal globular domains. Mutations in the gene encoding plectin ( PLEC ) cause two distinct autosomal recessive subtypes of epidermolysis bullosa: EB simplex (EBS) with muscular dystrophy (EBS‐MD), and EBS with pyloric atresia (EBS‐PA). Previous studies have demonstrated that loss of full‐length plectin with residual expression of the rodless isoform leads to EBS‐MD, whereas complete loss or marked attenuation of expression of full‐length and rodless plectin underlies the more severe EBS‐PA phenotype. However, muscular dystrophy has never been identified in EBS‐PA, not even in the severe form of the disease. Here, we report the first case of EBS associated with both pyloric atresia and muscular dystrophy. Both of the premature termination codon‐causing mutations of the proband are located within exon 32, the last exon of PLEC . Immunofluorescence and immunoblot analysis of skin samples and cultured fibroblasts from the proband revealed truncated plectin protein expression in low amounts. This study demonstrates that plectin deficiency can indeed lead to both muscular dystrophy and pyloric atresia in an individual EBS patient. © 2010 Wiley‐Liss, Inc.