title: Life-long course and molecular characterization of the original Dutch family with epidermolysis bullosa simplex with muscular dystrophy due to a homozygous novel plectin point mutation.
abstract: Plectin is one of the largest and most versatile cytolinker proteins known. Cloned and sequenced in 1991, it was later shown to have nonsense mutations in recessive epidermolysis bullosa with muscular dystrophy. A dominant mutation in the gene was found to cause epidermolysis bullosa simplex Ogna without muscular dystrophy. Here we report the DNA sequencing of the plectin gene (PLEC1) in a Dutch family originally described in 1972 as having epidermolysis bullosa with muscular dystrophy. The results revealed homozygosity for a new plectin nonsense mutation at position 13187 and its specific 8q24 marker haplotype profile. Western blotting of cultured fibroblasts and immunofluorescence microscopy of skin biopsy confirm that the plectin protein expression is grossly reduced or absent. A summary of the life-long clinical course of the two affected brothers homozygous for the new E1914X mutation is given.
authors.affiliation: Dermatological DNA Laboratory, Department of Dermatology, and Research Institute for Internal Medicine, Rikshospitalet University Hospital, Oslo, Norway. doeh@online.no
authors.forename: D
authors.initials: D
authors.lastname: Koss-Harnes
authors.forename: B
authors.initials: B
authors.lastname: Høyheim
authors.forename: M F
authors.initials: MF
authors.lastname: Jonkman
authors.forename: W P
authors.initials: WP
authors.lastname: de Groot
authors.forename: C J
authors.initials: CJ
authors.lastname: de Weerdt
authors.forename: B
authors.initials: B
authors.lastname: Nikolic
authors.forename: G
authors.initials: G
authors.lastname: Wiche
authors.forename: T
authors.initials: T
authors.lastname: Gedde-Dahl
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002908:Chronic Disease; D016110:Epidermolysis Bullosa Simplex / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005799:Genes, Dominant; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009664:Norway; D010375:Pedigree; D010641:Phenotype; D051190:Plectin; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051190:Plectin