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Mutation Analysis Of COL7A1 Gene In Two Chinese Families With Dystrophic Epidermolysis Bullosa Pruriginosa

Posted on:2008-12-09Degree:MasterType:Thesis
Country:ChinaCandidate:X L ChangFull Text:PDF
GTID:2144360218454231Subject:Dermatology and Venereology
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Background Dystrophic epidermolysis bullosa (DEB) is a group of heritable mechanobullous disorders characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy. It is inherited either in an autosomal dominant (DDEB) or in autosomal recessive (RDEB) pattern. Each form has different specific clinical presentations and severities. Both DDEB and RDEB are caused by mutations in the typeâ…¦collagen gene (COL7A1), which contributes to the maintaining of dermal-epidermal adhesion. To date, at least 320 mutations in the COL7A1 gene have been identified as the genetic basis of DEB.DEB pruriginosa is a distinct clinical type of DEB, characterized by skin fragility, blistering in early childhood and severe pruritus, nodular prurigo-like lichenified lesions after the first decade of life. DEB pruriginosa results from mutations of COL7A1 gene. About 30 distinct sequence variants in COL7A1 gene have been reported, most of which are glycine substitution mutations.Objective To identify the COL7A1 gene mutations in two Chinese patients with DEB pruriginosa. To analyze the clinical features of DEB families and the COL7A1 gene mutations of all DEB reported in China and explore the correlation between the genotypes and phenotypes.Methods Genomic DNA was extracted from peripheral blood of patients and family members with DEB pruriginosa and 100 unrelated normal controls. All 118 coding exons and intron-exon boundaries of COL7A1 gene were amplified using polymerase chain reaction (PCR). The PCR products were directly sequenced to detect the mutation. Case reports and papers about DEB since 1995 were searched by Chinese Biology Medicine (CBM) disc and the clinical features of DEB families and the gene mutations of all DEB cases were summarized and analyzed.Results One novel COL7A1 gene mutation (p.G2287E) and one mutation (p.G2287R) previously described were identified, both of which were heterozygous. In most of patients, the onset of the disease appeared since birth to 5 years old. The skin lesions were mainly located in the anticus tibialis,forearm and back. DEB is a clinically heterogeneous disorder showing different clinical menifetation. Most of COL7A1 gene mutations were glycine substitutions.Conclusions These two mutations (p .G2287R and p. G2287E) may be the underlying causes of DEB pruriginosa in the two families, not common polymorphism. DEB is a group of genodermatosis with various clinic variants and different expressivity. There are different phenotypes among the individuals. This study should be useful for gene therapy and genetic counseling for the patients and explore the correlation between the genotypes and phenotypes.
Keywords/Search Tags:dystrophic epidermolysis bullosa pruriginosa, type VII collagen, COL7A1 gene, mutation
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