Human Molecular Genetics, Vol 5, 1539-1546, Copyright © 1996 by Oxford University Press
L Pulkkinen, FJ Smith, H Shimizu, S Murata, H Yaoita, H Hachisuka, T Nishikawa, WH McLean and J Uitto
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.
ARTICLES
Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA 19107-5541, USA.
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