title: Molecular pathology of the basement membrane zone in heritable blistering diseases:: The paradigm of epidermolysis bullosa.
abstract: Epidermolysis bullosa (EB), a phenotypically heterogeneous group of skin fragility disorders, is characterized by blistering and erosions with considerable morbidity and mortality. Mutations in as many as 18 distinct genes expressed at the cutaneous basement membrane zone have been shown to be associated with the blistering phenotype, attesting to the role of the corresponding proteins in providing stable association of the epidermis to the dermis through adhesion at the dermo-epidermal basement membrane zone. Thus, different forms of EB have been highly instructive in providing information on the physiological functions of these proteins as integral components of the supramolecular adhesion complexes. In addition, precise information of the underlying genes and distinct mutations in families with EB has been helpful in subclassification of the disease with prognostic implications, as well as for prenatal testing and preimplantation genetic diagnosis. Furthermore, knowledge of the types of mutations is a prerequisite for application of allele-specific treatment approaches that have been recently developed, including read-through of premature termination codon mutations and chaperone-facilitated intracellular transport of conformationally altered proteins to proper physiologic subcellular location. Collectively, EB serves as a paradigm of heritable skin diseases in which significant progress has been made in identifying the underlying genetic bases and associated aberrant pathways leading from mutations to the phenotype, thus allowing application of precision medicine for this, currently intractable group of diseases.
authors: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: Jouni.Uitto@Jefferson.edu.
authors: Jouni
authors: J
authors: Uitto
authors: Department of Dermatology, University of Freiburg, Freiburg, Germany.
authors: Cristina
authors: C
authors: Has
authors: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA; Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
authors: Hassan
authors: H
authors: Vahidnezhad
authors: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Leila
authors: L
authors: Youssefian
authors: Department of Dermatology, University of Freiburg, Freiburg, Germany.
authors: Leena
authors: L
authors: Bruckner-Tuderman
mesh_terms: D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology*; D024143:Collagen Type VII / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004820:Epidermolysis Bullosa / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D019836:Preimplantation Diagnosis; D011296:Prenatal Diagnosis; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology*
chemical_list: C569053:COL7A1 protein, human; D024143:Collagen Type VII; D016326:Extracellular Matrix Proteins
keywords: Cutaneous basement membrane zone; Epidermolysis bullosa; Heritable blistering diseases; Type VII collagen