ABSTRACT
Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X-linked recessive, autosomal dominant or autosomal recessive inheritance traits. The X-linked form of HED is caused by mutations in the EDA gene, while autosomal forms result from mutations in either EDAR or EDARADD genes. Regarding recessive mutations in the EDAR gene, the pathomechanisms have been well characterized. However, it has remained largely unknown how dominant mutations in the EDAR cause HED. In this study, we performed in vitro analyses for a dominant EDAR gene mutation, p.F398*, as a representative. We showed that the p.F398* mutant EDAR completely lost its affinity to EDARADD, and suppressed the downstream nuclear factor-κB activation induced by wild-type EDAR in a dominant-negative manner. Furthermore, we demonstrated that the mutant EDAR was capable of binding with the wild-type EDAR, which led to reduced interaction between the wild-type EDAR and EDARADD. Our findings not only underscore an essential role of the interaction between EDAR and EDARADD in ectodermal development, but also disclose, in part, the molecular basis of autosomal dominant HED.
Subject(s)
Ectodermal Dysplasia 1, Anhidrotic/genetics , Edar Receptor/genetics , Edar-Associated Death Domain Protein/metabolism , Genes, Dominant/genetics , Ectodermal Dysplasia 1, Anhidrotic/pathology , Edar Receptor/metabolism , HEK293 Cells , Humans , MutationSubject(s)
Dermatitis, Atopic/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/diagnosis , Hypotrichosis/diagnosis , Keratoderma, Palmoplantar/diagnosis , Phenotype , Adult , Asian People/genetics , Child , DNA Mutational Analysis , Dermatitis, Atopic/genetics , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Exons , Humans , Hypotrichosis/genetics , Keratoderma, Palmoplantar/genetics , Male , Mutation , Young AdultSubject(s)
Acute Generalized Exanthematous Pustulosis/etiology , Antifungal Agents/adverse effects , Candidiasis, Cutaneous/drug therapy , Psoriasis/pathology , Terbinafine/adverse effects , Acute Generalized Exanthematous Pustulosis/immunology , Acute Generalized Exanthematous Pustulosis/pathology , Aged, 80 and over , Candida/immunology , Candida/isolation & purification , Candidiasis, Cutaneous/immunology , Candidiasis, Cutaneous/microbiology , Disease Progression , Humans , Male , Psoriasis/immunology , Skin/drug effects , Skin/pathologyABSTRACT
We present a case of Fournier's gangrene secondary to rectal cancer that was managed with perineal reconstruction using a posterior thigh flap after debridement and tumor resection. A 67-year-old man was admitted with disturbed consciousness as well as hip and right thigh pain. His perineal and gluteal skin was necrotic. CT revealed subcutaneous emphysema that had spread from the rectum to the gluteal region and right thigh. We diagnosed him with Fournier's gangrene, and then removed the necrotic tissue and constructed a sigmoidostomy. A diagnosis of rectal cancer was later confirmed. Fifty-nine days after the initial operation, a laparoscopic abdominoperineal resection was performed. The perineal defect was repaired using a posterior thigh flap with the gluteus maximus. There were no postoperative complications, and the patient was discharged ahead of schedule. We concluded that the use of a posterior thigh flap is a good choice for perineal reconstruction, because it is simple to perform, can cover a large area, and has a low risk of infection.
