家族性原发性皮肤淀粉样变与先天性厚甲症的基因突变研究-皮肤病与性病学专业论文.docxVIP

Ab Abstract PAGE PAGE IV ABSTRACT Background: Both familial primary localized cutaneous amyloidosis (FPCA) and pachyonychia congenita(PC) are rarely autosomal-dominant genodermatosis. FPCA is characterized by papule occurring typically over the shins with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPCA has been mapped early to chromosome 5 and 11 pathogenic missense mutations in the OSMR gene, which encodes the interleukin-6 family cytokine receptor oncostatin M-specific receptor beta (OSMRβ), were reported. The precise pathogenesis of FPCA is unclear and a effective and treatment of FPCA is absent in clinic. Also PC Ⅱtype is a rare disease which is associated with palmoplantar hyperkeratosis, natal tooth and steatocystoma multiplex. So far, K17 gene and K6b gene have been reported as part of the pathogenesis of PC. There is no effective therapy for pachyonychia congenita. Objective: To identify mutation in the OSMR gene in a pedigree with FPCA and the the K17 and K6b gene in a pedigree with PC Ⅱtype. Methods: We collected a pedigree with FPCA and a pedigree with PC. We executed congo red staining in lesional skin biopsy of the proband of FPCA. Genomic DNA was respectively extracted from peripheral blood samples obtained from the two pedigrees, and subjected to PCR for the amplification of encoding exons and their flanking sequences of the relevant gene followed by Sanger sequencing. The sequencing results were analyzed with BioEdit Sequence Alignment Editor. We performed gene mutation detection of the other members of the family and 50 normal subjects to rule out mutations polymorphism after preliminary founding the locus. Results: 1.A pedigree including 7 individuals affected with FPCA was enrolled in this study. The pedigree consists of 47 members. Histopathology of lesional skin showed orange crumb material in the superficial papillary dermis by congo red staining. A heterozygous m