A HOMOZYGOUS NONSENSE MUTATION IN THE ALPHA-3 CHAIN GENE OF LAMININ-5(LAMA3) IN HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA - PRENATAL EXCLUSION IN A FETUS AT RISK

Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been establis hed as the genetic basis for the inherited blistering skin disorder, H erlitz junctional epidermolysis bullosa (H-JEB). In this study, we per formed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain gene (LAMA3) consi sting of a homozygous C-to-T transition resulting in a premature termi nation codon (CGA --> TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysi s was used to perform DNA-based prenatal diagnosis from a chorionic vi llus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetu s was predicted to be genotypically normal with respect to the LAMA3 m utation. (C) 1995 Academic Press, Inc.