DNA based prenatal testing for the skin blistering disorder epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder in which m ild physical trauma leads to blistering. The phenotype of the disorder is v ariable, from relatively mild affecting only the hands and/or feet, to very severe with widespread blistering. For the severest forms of EBS there is a demand for prenatal diagnosis which until now has involved a fetal skin b iopsy in the second trimester. The identification of mutations in the genes encoding keratins K5 and K14 as the cause of EBS opens up the possibility of much earlier diagnosis of the disease. We report here four cases in whic h prenatal testing was performed. In three of the cases the genetic lesions were unknown at the start of the pregnancy, requiring the identification o f the causative mutation prior to testing fetal DNA. In two of the four cas es novel mutations were identified in K14 and in the two remaining families , a previously identified type of mutation was found. Fetal DNA, obtained b y chorionic villus sampling or amniocentesis, was analysed for the identifi ed mutations. Three of the DNA samples were found to be normal; a mutant K1 4 allele was identified in the fourth case and the pregnancy was terminated . These results demonstrate the feasibility of DNA-based prenatal testing f or EBS in families where causative mutations can be found. Copyright (C) 20 00 John Wiley & Sons, Ltd.