title: Prenatal diagnosis of dominant dystrophic epidermolysis bullosa, by COL7A1 molecular analysis.
abstract: We report the first direct molecular prenatal diagnosis, undertaken for the autosomal dominant form of dystrophic epidermolysis bullosa (DDEB). The proband had a moderately severe form of DDEB, with episodic blistering of skin and mucosal involvement. Diagnostic histopathological examination, using electron microscopy to evaluate skin from a fresh blister, demonstrated a zone of cleavage beneath the epidermal-dermal junction, thereby assigning the EB as dystrophic. DNA analysis of COL7A1, the gene encoding type VII collagen, identified a heterozygous transversion (G to A) in the triple helix domain (G2043R). For any subsequent pregnancy, the affected mother and the unaffected father of the proband requested prenatal prediction, which was thereafter carried out in DNA extracted from a chorionic villus sample obtained at 11 weeks of gestation. Restriction enzyme analysis of COL7A1 exons 73 and 74 amplified by PCR, demonstrated the presence of the G2043R mutation, and the pregnancy was subsequently terminated. Molecular analysis of DNA extracted from fetal tissues confirmed the prenatal prediction.
authors.affiliation: Division of Chemical Pathology, Queensland Health Pathology Service, Royal Brisbane Hospitals, Queensland, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Klingberg
authors.forename: R
authors.initials: R
authors.lastname: Mortimore
authors.forename: J
authors.initials: J
authors.lastname: Parkes
authors.forename: J E
authors.initials: JE
authors.lastname: Chick
authors.forename: A E
authors.initials: AE
authors.lastname: Clague
authors.forename: D
authors.initials: D
authors.lastname: Murrell
authors.forename: D
authors.initials: D
authors.lastname: Weedon
authors.forename: I A
authors.initials: IA
authors.lastname: Glass
mesh_terms: D001483:Base Sequence; D002648:Child; D015193:Chorionic Villi Sampling; D003094:Collagen / Q000235:genetics*; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D016108:Epidermolysis Bullosa Dystrophica / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA
chemical_list: D003094:Collagen; C025651:CCCGGG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific