Novel PLEC Variant Causes Only Mild Skin Fragility, but Pyloric Atresia, Muscular Dystrophy and Urological Manifestations.
Novel PLEC Variant Causes Only Mild Skin Fragility, but Pyloric Atresia, Muscular Dystrophy and Urological Manifestations. Acta Derm Venereol. 2019 Sep 12;: Authors: Valari M, Theodoraki M, Loukas I, Gkantseva-Patsoura S, Karavana G, Falaina V, Lykopoulou L, Pons R, Athanasiou I, Wertheim-Tysarowska K, Kanaka-Gantenbein C, Kiritsi D PMID: 31513275 [PubMed - as supplied by publisher]
Plectin is a giant multifunctional cytolinker protein (500 kDa) expressed in several tissues with essential roles in striated and smooth muscles, epithelia and nerve. It is a component of hemidesmosomes, desmosomes and focal adhesion contacts where it interacts with actin and intermediate filaments. Pathogenic variants in the PLEC1 gene lead to a group of diseases including epidermolysis bullosa (simplex ogna with or without muscular dystrophy, myasthenic syndrome, or pyloric atresia) and isolated limb-girdle muscular dystrophy.
Authors: Reimer A, Has C Abstract Syndromic disorders with skin fragility belong to different groups of genodermatoses: epidermolysis bullosa (EB), Ehlers-Danlos syndrome and porphyria. The genetic defects mainly concern structural proteins which assure the mechanical stability of the skin and other tissues. Depending on the expression pattern of the affected protein in the skin, cutaneous fragility may manifest as superficial erosions, blisters, wounds, wound healing defects or scars. Extracutaneous manifestations are manifold and involve the heart, skeletal muscles, intestine, kidneys, blood vessels or the skelet...
In January, 2018, Academic Press published my bookPrecision Medicine and the Reinvention of Human Disease. This book has an excellent " look inside " at itsGoogle book site, which includes the Table of Contents. In addition, I thought it might be helpful to see the topics listed in the Book's index. Note that page numbers followed by f indicate figures, t indicate tables, and ge indicate glossary terms.AAbandonware, 270, 310geAb initio, 34, 48ge, 108geABL (abelson leukemia) gene, 28, 58ge, 95 –97Absidia corymbifera, 218Acanthameoba, 213Acanthosis nigricans, 144geAchondroplasia, 74, 143ge, 354geAcne, 54ge, 1...
Plectin, a giant multifunctional cytolinker protein, plays a crucial role in orchestrating intermediate filament networks in a wide variety of tissues, as epithelia, skeletal muscle and heart. Mutations of the plectin gene (PLEC) on chromosome 8q24 cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), EBS-MD with myasthenic features, EBS with pyloric atresia, EBS-Ogna, and LGMD2Q. Here we report an Italian family with a distinctive muscle phenotype and autosomal recessive transmission in which Whole Exome Sequencing identified homozygous mutations in PLEC gene.
We report on a Turkish patient with congenital myopathy with a fiber type disproportion and central myonuclei comparable to a centronuclear myopathy and skin blistering (epidermolysis bullosa simplex, EBS) due to a novel homozygous mutation in the plectin gene, a cytoskeleton-membrane anchorage protein. So far, EBS has only been described to be associated with congenital or limb girdle muscular dystrophy, myasthenic syndrome, or pyloric atresia. A clubfoot and hypotonia were noted directly at birth, skin blistering was identified shortly after cast treatment of the foot malposition.
Abstract Hereditary epidermolysis bullosa (EB) is a heterogeneous group of rare genetic diseases characterized by fragile skin and/or mucous membrane, and it may be either local or generalized. It is caused by mutations in genes encoding different proteins involved mainly in the structure and function of the dermal-epidermal junction. Nineteen genes have so far been identified. They are classified by level of skin cleavage (from top to bottom) into four groups: EB simplex, junctional EB, dystrophic EB and Kindler syndrome. Clinically suspected diagnosis is confirmed by immunohistochemical examination of a skin bio...
We present two cases of EB with significant urologic involvement resulting from mutations in plectin.
Epidermolysis bullosa simplex (EBS) is a group of congenital skin fragility disorders characterized by intraepidermal skin detachment. PLEC, encoding plectin, is one of the causative genes responsible for EBS. Plectin deficiency is responsible for two autosomal recessive EBS subtypes: EBS with muscular dystrophy (EBS-MD) and EBS with pyloric atresia (EBS-PA). Plectin is a linker protein between hemidesmosomes and intermediate filaments. Plectin harbors a central rod domain which mediates homodimer formation.
Epidermolysis bullosa simplex (EBS) is caused by autosomal recessive and dominant mutations in PLEC in 8% of all cases. In humans, eight distinct plectin isoforms have been identified arising from tissue specific translation, differing in the first exon. Additionally, alternative splicing of exon 31 results in a rodless plectin variant, seen in patients affected with EBS with muscular dystrophy (EBS-MD). Complete absence of plectin leads to a severe phenotype with generalized blistering and pyloric atresia (EBS-PA), and early mortality.
We report the first cases of autosomal-recessive EBS from P1a deficiency affecting skin, while mucous membranes, heart and muscle are spared. The dominant expression of the P1a isoform in epidermal basal cell layer and cultured keratinocytes suggests that mutations in the first exon of isoform 1a cause skin-only EBS without extracutaneous involvement. Our study characterizes yet another of the eight isoforms of plectin and adds a tissue-specific phenotype to the spectrum of ‘plectinopathies' produced by mutations of unique first exons of this gene.