Progress in epidermolysis bullosa: the phenotypic spectrum of plectin mutations.
ABSTRACT Plectin, a large multidomain adhesive protein with versatile binding functions, is expressed in a number of tissues and cell types. In the skin, plectin is a critical component of hemidesmosomes, interacting with keratin intermediate filaments and beta4 integrin. Mutations in the plectin gene (PLEC1) result in fragility of skin, demonstrating blister formation at the level of hemidesmosomes. These blistering disorders belong to the spectrum of epidermolysis bullosa (EB) phenotypes, and three distinct variants because of plectin mutations have been identified. First, EB with muscular dystrophy, an autosomal recessive syndrome, is frequently caused by premature termination codon-causing mutations leading to the absence of plectin both in the skin and in the muscle. Second, a heterozygous missense mutation (R2110W) in PLEC1 has been documented in patients with EB simplex of the Ogna type, a rare autosomal dominant disorder. Finally, recent studies have disclosed plectin mutations in patients with EB with pyloric atresia, an autosomal recessive syndrome, frequently with lethal consequences. Collectively, these observations attest to the phenotypic spectrum of plectin mutations, and provide the basis for accurate genetic counselling with prognostic implications, as well as for prenatal diagnosis in families at the risk of recurrence of the disease.
- Journal of Vascular and Interventional Radiology 01/1996; 7(1):375-376. · 2.15 Impact Factor
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ABSTRACT: Mutations in plectin, a widely expressed giant cytolinker protein can lead to different diseases mostly with signs of muscular dystrophy (MD) and skin blistering. The only report of plectin-related disease without skin involvement is limb-girdle muscular dystrophy type 2Q (LGMD2Q) phenotype, showing early-onset limb-girdle muscular dystrophy symptoms with progressive manner and no cranial muscle involvement. Here, we report a non-consanguineous Iranian family with two affected sisters showing progressive limb and ocular muscle weakness. Whole Exome Sequencing (WES) led to identification of a compound heterozygous mutations, p.Gln1022Ter (c.3064C>T) and p.Gly3835Ser (c.11503G>A), in PLEC gene. To the best of our knowledge, this would be the first report of a patient with LGMD and myasthenic symptoms without any skin involvement, caused by plectinopathy. This observation extends the phenotypic spectrum of PLEC related diseases and suggests a variable expression of the PLEC- related symptoms.Archives of Iranian medicine 01/2015; 18(1):60-4. · 1.11 Impact Factor
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ABSTRACT: Plectin mutations have been reported in epidermolysis bullosa simplex with muscular dystrophy. We report the first case of left ventricular non-compaction in an 18 year old male with epidermolysis bullosa simplex with muscular dystrophy. The patient was diagnosed with epidermolysis bullosa simplex after blistering was noted at birth. Motor function difficulties were first recognized at age 11, however the patient was lost to follow up. He was re-evaluated at age 17 and demonstrated significant ptosis, ophthalmoparesis, and pharyngeal muscle weakness. He had predominant proximal muscle weakness with the inability to raise arms against gravity. He was ambulatory for short distances but lost the ability to rise from floor at 14 years. He was subsequently diagnosed with epidermyolysis bullosa simplex with muscular dystrophy and a PLEC1 mutation. Screening cardiovascular imaging revealed a diagnosis of isolated left ventricular non-compaction. This case highlights the potential for delayed onset muscular dystrophy in patients with epidermolysis bullosa simplex. Furthermore, this case also underscores the importance of long term, routine cardiac evaluation, including imaging and electrophysiologic evaluation, in patients with epidermolysis bullosa simplex with muscular dystrophy as the cardiac phenotype appears to parallel the variable severity and age of onset that characterize the neuromuscular phenotype.Neuromuscular Disorders 10/2014; 25(2). · 3.13 Impact Factor