Disease relevance of Epidermolysis Bullosa, Junctional

• Primary beta4-null keratinocytes, obtained from a newborn suffering from lethal junctional epidermolysis bullosa, were stably transduced with retroviruses carrying a full-length beta4 cDNA or a beta4 cDNA with phenylalanine substitutions at Tyr-1422 and Tyr-1440 [1].
• The data suggest that different COL17A1 mutations and their combinations can result in a spectrum of biologic and clinical phenotypes of not only generalized atrophic benign epidermolysis bullosa, but also localized junctional epidermolysis bullosa [2].
• Mutations in the three genes (LAMA3, LAMB3, LAMC2) encoding the laminin-5 chains cause junctional epidermolysis bullosa, a clinically and genetically heterogeneous blistering skin disease [3].
• BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB) [4].

High impact information on Epidermolysis Bullosa, Junctional

• Mutations in the genes encoding integrin beta 4 and chains of laminin-5 have been implicated in junctional epidermolysis bullosa [5].
• Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5) [6].
• A homozygous mutation in the integrin alpha6 gene in junctional epidermolysis bullosa with pyloric atresia [7].
• Previous studies have correlated the Herlitz junctional epidermolysis bullosa (H-JEB) to an altered expression of the basement membrane component nicein/kalinin [8].
• These studies show that antiepiligrin autoantibodies are a specific marker for a novel autoimmune blistering disease and that the epidermal basement membrane antigen absent in patients with lethal junctional epidermolysis bullosa is epiligrin [9].

Chemical compound and disease context of Epidermolysis Bullosa, Junctional

• Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition [10].
• Phenytoin therapy for junctional epidermolysis bullosa [11].

Biological context of Epidermolysis Bullosa, Junctional

• In this study, we report a patient with a form of junctional epidermolysis bullosa with skin fragility and dental anomalies who is a compound heterozygote for a novel combination of mutations, ie, a glycine substitution mutation in one allele and an internal duplication in the other allele of COL17A1 [10].
• Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa [12].
• Comparative analysis of the nucleotide sequence of the full-length gamma2 cDNA isolated by reverse transcription polymerase chain reaction amplification of total RNA purified from the epithelium of a junctional epidermolysis bullosa foal and a healthy control disclosed a homozygous basepair insertion (1368insC) in the affected animal [13].
• Analysis of the LAMB3 gene in a junctional epidermolysis bullosa patient reveals exonic splicing and allele-specific nonsense-mediated mRNA decay [14].
• Amniocentesis and fetal skin biopsies were performed at 18 weeks of gestation in a fetus at risk for autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive junctional epidermolysis bullosa (EBJ) with pyloric atresia [15].

Anatomical context of Epidermolysis Bullosa, Junctional

• In beta4-deficient pyloric atresia associated with junctional epidermolysis bullosa (PA-JEB) keratinocytes, CD151 and alpha3beta1 are clustered together at the basal cell surface in association with patches of laminin-5 [16].
• Deficiency of the integrin beta 4 subunit in junctional epidermolysis bullosa with pyloric atresia: consequences for hemidesmosome formation and adhesion properties [17].
• We also report a direct DNA-based prenatal exclusion of Herlitz junctional epidermolysis bullosa in a pregnancy at risk using a chorionic villus biopsy and allele-specific oligomer hybridization from polymerase chain reaction-amplified genomic DNA [18].

Gene context of Epidermolysis Bullosa, Junctional

• The blistering disorder, lethal junctional epidermolysis bullosa (JEB), can result from mutations in the LAMB3 gene, which encodes laminin 5 beta3 (beta3) [19].
• A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa [20].
• Localized and generalized Mitis types as well as the majority of tested families with the Herlitz type of junctional epidermolysis bullosa appeared not to be similarly linked or associated to LAMC1 [21].
• Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous splice-site mutation in a patient with junctional epidermolysis bullosa associated with pyloric atresia [22].
• Integrin beta 4 mutations associated with junctional epidermolysis bullosa with pyloric atresia [23].

Analytical, diagnostic and therapeutic context of Epidermolysis Bullosa, Junctional

• Comparative immunoprecipitation studies of patient sera, P1E1, and GB3 monoclonal antibody show that epiligrin is identical to the antigen (i.e., BM600 or GB3 antigen) previously reported to be absent from the skin of patients with lethal junctional epidermolysis bullosa, an inherited subepidermal blistering disease [9].
• In this study, we searched for mutations in these genes in two patients with nonlethal forms of junctional epidermolysis bullosa using polymerase chain reaction amplification of genomic DA, followed by heteroduplex analysis and direct automated nucleotide sequencing [24].
• Hematopoietic stem cell transplantation and subsequent 80% skin exchange by grafts from the same donor in a patient with Herlitz disease [25].
• Immunofluorescence analysis using monoclonal antibodies against BP180 (and laminin-5) may allow early subtyping, which is of prognostic significance, in children born with junctional epidermolysis bullosa [26].

References