title: DNA based prenatal testing for the skin blistering disorder epidermolysis bullosa simplex.
abstract: Epidermolysis bullosa simplex (EBS) is a skin fragility disorder in which mild physical trauma leads to blistering. The phenotype of the disorder is variable, 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 biopsy 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 which prenatal testing was performed. In three of the cases the genetic lesions were unknown at the start of the pregnancy, requiring the identification of the causative mutation prior to testing fetal DNA. In two of the four cases novel mutations were identified in K14 and in the two remaining families, a previously identified type of mutation was found. Fetal DNA, obtained by chorionic villus sampling or amniocentesis, was analysed for the identified mutations. Three of the DNA samples were found to be normal; a mutant K14 allele was identified in the fourth case and the pregnancy was terminated. These results demonstrate the feasibility of DNA-based prenatal testing for EBS in families where causative mutations can be found.
authors.affiliation: CRC Cell Structure Research Group, Cancer Research Campaign Laboratories, Department of Anatomy & Physiology, University of Dundee, Dundee, U.K. E.L.Rugg@mds.qmw.ac.uk
authors.forename: E L
authors.initials: EL
authors.lastname: Rugg
authors.forename: D
authors.initials: D
authors.lastname: Baty
authors.forename: C S
authors.initials: CS
authors.lastname: Shemanko
authors.forename: G
authors.initials: G
authors.lastname: Magee
authors.forename: S
authors.initials: S
authors.lastname: Polak
authors.forename: R
authors.initials: R
authors.lastname: Bergman
authors.forename: T
authors.initials: T
authors.lastname: Kadar
authors.forename: M
authors.initials: M
authors.lastname: Boxer
authors.forename: T
authors.initials: T
authors.lastname: Falik-Zaccai
authors.forename: Z
authors.initials: Z
authors.lastname: Borochowitz
authors.forename: E B
authors.initials: EB
authors.lastname: Lane
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis*; D004252:DNA Mutational Analysis; D004817:Epidermis / Q000473:pathology; D016110:Epidermolysis Bullosa Simplex / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006639:Histidine; D006801:Humans; D053547:Keratin-14; D015603:Keratinocytes / Q000473:pathology; D007633:Keratins / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D017422:Sequence Analysis, DNA; D014443:Tyrosine
chemical_list: C507540:KRT14 protein, human; D053547:Keratin-14; D014443:Tyrosine; D006639:Histidine; D007633:Keratins; D004247:DNA