title: Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex.
abstract: 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.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. natsuga@med.hokudai.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Natsuga
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishie
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinkuma
authors.forename: Ken
authors.initials: K
authors.lastname: Arita
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Makiko
authors.initials: M
authors.lastname: Ohyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kambara
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hirako
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004065:Digestive System Abnormalities / Q000150:complications / Q000235:genetics*; D016110:Epidermolysis Bullosa Simplex / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000150:complications / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D051190:Plectin / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011708:Pylorus / Q000002:abnormalities*; D012867:Skin / Q000378:metabolism
chemical_list: C495332:PLEC protein, human; D051190:Plectin