Has Cristina, Bruckner-Tuderman Leena
Department of Dermatology, Medical Center-University of Freiburg, Freiburg 79104, Germany; email:
Annu Rev Genomics Hum Genet. 2014;15:245-68. doi: 10.1146/annurev-genom-090413-025540. Epub 2014 May 29.
Genetic skin fragility manifests with diminished resistance of the skin and mucous membranes to external mechanical forces and with skin blistering, erosions, and painful wounds as clinical features. Skin fragility disorders, collectively called epidermolysis bullosa, are caused by mutations in 18 distinct genes that encode proteins involved in epidermal integrity and dermal-epidermal adhesion. The genetic spectrum, along with environmental and genetic modifiers, creates a large number of clinical phenotypes, spanning from minor localized lesions to severe generalized blistering, secondary skin cancer, or early demise resulting from extensive loss of the epidermis. Laboratory investigations of skin fragility have greatly augmented our understanding of genotype-phenotype correlations in epidermolysis bullosa and have also advanced skin biology in general. Current translational research concentrates on the development of biologically valid treatments with therapeutic genes, cells, proteins, or small-molecule compounds in preclinical settings or human pilot trials.
遗传性皮肤脆弱表现为皮肤和黏膜对外界机械力的抵抗力减弱，临床特征为皮肤水疱、糜烂和疼痛性伤口。统称为大疱性表皮松解症的皮肤脆弱性疾病，是由18个不同基因的突变引起的，这些基因编码参与表皮完整性和真皮-表皮黏附的蛋白质。遗传谱以及环境和遗传修饰因子产生了大量的临床表型，范围从轻微的局限性病变到严重的全身性水疱、继发性皮肤癌，或因表皮大量丧失导致的早期死亡。对皮肤脆弱性的实验室研究极大地增进了我们对大疱性表皮松解症基因型-表型相关性的理解，也推动了整体皮肤生物学的发展。当前的转化研究集中在临床前环境或人体试点试验中，利用治疗性基因、细胞、蛋白质或小分子化合物开发具有生物学有效性的治疗方法。
