Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy
| Autor: | Hiroshi Hachisuka, W.H. Irwin McLean, Hideo Yaoita, Takeji Nishikawa, Satoru Murata, Hiroshi Shimizu, Frances J.D. Smith, Leena Pulkkinen, Jouni Uitto |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Proband Molecular Sequence Data macromolecular substances Biology medicine.disease_cause Muscular Dystrophies Frameshift mutation Mice Epidermolysis bullosa simplex Intermediate Filament Proteins Genetics medicine Animals Humans Muscular dystrophy Molecular Biology Genetics (clinical) Mutation Hemidesmosome Homozygote General Medicine Plectin medicine.disease Pedigree Epidermolysis Bullosa Simplex Female Epidermolysis bullosa Gene Deletion |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/5.10.1539 |
| Popis: | In a distinct autosomal recessive variant of epidermolysis bullosa, EB-MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|