Mutations in plectin a protein involved in hemidesmosome integrity and function, are associated with subtypes of EB, including EB with pyloric atresia and EB with muscular dystrophy.
The most common disease caused by mutations in the human plectin gene, epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is characterized by severe skin blistering and progressive muscular dystrophy.
Due to the ubiquitous presence of plectin in mammalian tissues, EBS from recessive plectin mutations is always associated with extracutaneous involvement including muscular dystrophy, pyloric atresia and cardiomyopathy.
Phenotype-genotype analysis has suggested that EBS-MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS-PA to mutations outside this domain.
Mutations in the plectin gene (PLEC1) cause epidermolysis bullosa simplex (EBS), which may associate with muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA).
Autosomal recessive forms of EBS associated with extracutaneous manifestations, such as muscular dystrophy (MIM 226670) or pyloric atresia (MIM 612138), have been linked to genetic mutations in the gene for plectin (PLEC).
We conclude that PLEC1 should be considered in the differential diagnosis of congenital muscular dystrophies and myasthenic syndromes, even in the absence of prominent skin involvement.
These results validate chorionic villi immunofluorescence examination as a tool for prenatal diagnosis of PA-JEB and PA-EBS and indicate that this procedure could be devised for EB with muscular dystrophy, which is also associated with genetic mutations in plectin.
Instead, PCR amplification followed by heteroduplex scanning and/or direct nucleotide sequencing revealed homozygous mutations in the plectin gene (PLEC1), encoding another hemidesmosomal protein previously linked to EB with 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 complete lack of protein expression, which may be attributed to a nonsense-mediated plectin mRNA decay, is likely to cause muscular dystrophy and other multisystem involvement later in life.
The recessive simplex types include EB with muscular dystrophy due to abnormal plectin, EB without muscular dystrophy in patients homozygous for K14 gene abnormalities, and skin fragility syndrome, with formation of acantholytic vesicles within the epidermis due to PKP1 gene mutations.
Genetic mutations in plectin, a cytoskeleton linker protein expressed in a large variety of tissues including skin, muscle, and nerves, cause epidermolysis bullosa simplex with muscular dystrophy, a recessive inherited disease characterized by blistering of the skin and late onset of muscular dystrophy, and Ogna epidermolysis bullosa simplex, a rare dominant inherited form of epidermolysis bullosa simplex with no muscular involvement.
Because plectin deficiency is associated with muscular dystrophy, molecular diagnostics of the plectin gene provides prognostic value in evaluation of these patients who appear to be at risk to develop muscular dystrophy.
Epidermolysis bullosa simplex associated with late onset of muscular dystrophy has been found to show defective expression of plectin, an intracytoplasmic protein in hemidesmosomes.
Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests.
Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy and the use of protein truncation test for detection of premature termination codon mutations.