BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases. 相似文献
Objectives: Using our serological diagnostic criteria, we selected 105 Japanese patients with epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease (AIBD) reacting with type VII collagen, from our cohort of 5063 AIBD patients.
Methods: We examined the patients clinically and immunologically.
Results: We found diversity of clinical manifestations in both cutaneous and oral mucosal lesions and a high rate of inflammatory-type EBA patients in Japan. Common treatments were systemic steroids, followed by immunosuppressives, DDS, tetracycline/minocycline and colchicine. Immunological studies revealed that indirect immunofluorescence of 1M-NaCl-split skin, immunoblotting of dermal extract, and type VII collagen ELISA were sensitive methods, with possible multiplicity of circulating autoantibodies against other basement membrane autoantigens.
Conclusion: The present study analyzed the largest cohort of EBA patients, confirming the scarcity of EBA (only 105 of the 5063 AIBD patients), and showed that the three serological tests are useful for the diagnosis of EBA. 相似文献
Epidermolysis bullosa (EB) is a relatively rare inherited disorder, which includes blister and vesicle formation on the skin and mucous membranes as a result of trauma or heat. There are different forms of this disorder. Mild manifestations are relatively uncomfortable, usually involving the knees, elbows, and fingers. Severe forms of this disease compromise normal functioning of multiple organs, which may result in premature death. The lack of a specific treatment to cure EB makes genetic counseling and prenatal diagnosis of primary importance to control this disorder. Three case histories of persons with dystrophic recessive epidermolysis bullosa are reported, focusing on appropriate dental care for patients with EB. 相似文献
Abstract The Herlitz type of junctional epidermolysis bullosa (H-JEB) is a serve blistering disease affecting the skin and mucous membranes, which is usually lethal within the first year of life. The laminin 5 genes have been implicated as candidate genes for most patients with H-JEB. Recently two hotspot mutations were delineated in the LAMB3 gene, known as R42X and R635X, and have been noted in over 50% of mutant LAMB3 alleles. Here, we present a case of H-JEB of Hungarian origin with a neonatal lethal outcome. Monoclonal antibody staining showed a lack of expression of the laminin 5β3 chain, as a possible result of a mutation in one of the laminin 5 genes. Screening of the family identified the previously described mutation R635X in exon 14 of LAMB3 in each of the parents and one healthy sibling in the heterozygous form, while proband was homozygous for R635X, and the other sibling proved to be genotypically normal. These results underscore the widespread prevalence of R635X in H-JEB cases form around the world. 相似文献
Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is characterized by recurrent mucocutaneous blistering with non-healing ulcers which are often complicated by squamous cell carcinoma (SCC). Despite having as high as 80% death rate from SCC, RDEB still does not have an effective treatment. We report on the efficacy of single follicular unit extract (FUE) grafting to heal chronic ulcers of intermediate RDEB in a 54-year-old woman with extensive chronic wounds covering around 30% of the body surface area. On Day 17 post first graft session, the area of treated ulcers on her right upper back was reduced by 80%. Immunofluorescence study revealed positive type VII collagen expression along the epidermal and follicular basement membrane zone in the donor and recipient sites. A few grafted follicles continued to grow hair on the recipient sites. A total of 360 FUEs were grafted in nine sessions over five years, resulting in healing of most treated ulcers and reduced significantly her time for daily wound dressing. Importantly, FUE grafting using patient's own scalp follicles does not require any laboratory manipulation. It is safe and easy to perform. Autologous follicular grafting appears efficacious for healing of recalcitrant wounds and provides an innovative solution for RDEB patients with such wounds. 相似文献
AbstractA key function of human skin is the formation of a structural barrier against the external environment. In part, this is achieved through the formation of a cornified cell envelope derived from a stratified squamous epithelium attached to an epithelial basement membrane. Resilient in health, the structural integrity of skin can become impaired or break down in a collection of inherited skin diseases, referred to as the blistering genodermatoses. These disorders arise from inherited gene mutations in a variety of structural and signalling proteins and manifest clinically as blisters or erosions following minor skin trauma. In some patients, blistering can be severe resulting in significant morbidity. Furthermore, a number of these conditions are associated with debilitating extra-cutaneous manifestations including gastro-intestinal, cardiac, and ocular complications. In recent years, an improved understanding of the molecular basis of the blistering genodermatoses has led to better disease classification and genetic counselling. For patients, this has also advanced translational research with the advent of new clinical trials of gene, protein, cell, drug, and small molecule therapies. Although curing inherited blistering skin diseases still remains elusive, significant improvements in patients’ quality of life are already being achieved. 相似文献
Epidermolysis bullosa (EB), a heterogeneous group of hereditary diseases, varies in mode of inheritance, extent, severity, and presence or absence of scarring and dystrophy. Fourteen cases (13 in infants and 1 in a young adult) were studied. Subtyping by ultrastructural findings in normal and blistered skin biopsies was as follows: EB simplex (2), EB letalis (3), EBD dominant (2), and EBD recessive (7). One case diagnosed as recessive dystrophic by electron microscopy (EM) followed a benign course with little scaring and was re-classified clinically and after reviewing the EM as dominant dystrophic. Defining the level of bulla formation by EM allowed accurate diagnosis of subtypes. In 6 patients with EBD recessive, normal and bullous skin showed collagenolysis and no anchoring fibrils. In patients with EBD dominant, rudimentary fibrils were noted in normal skin. Whether absence of anchoring fibrils is primary or secondary in these two types and the role of collagenolysis remain unresolved. 相似文献