A Homozygous Nonsense Mutation in the α3 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 chaises (α3, β3, and γ2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the α3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA → TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation.