Genetic basis of lethal junctional epidermolysis bullosa in an affected fetus: implications for prenatal diagnosis in one family.

Fetal skin biopsy at 20 weeks' gestation in a woman at risk for a child with the lethal skin-blistering disorder junctional epidermolysis bullosa (Herlitz) confirmed an affected fetus. Genomic DNA from the aborted fetus was examined for mutations in laminin 5, a macromolecule involved in adhesion at the dermal-epidermal junction, and a candidate protein in this condition. Polymerase chain reaction (PCR) amplification of exon 10 and parts of the flanking introns of the gene encoding the beta 3 chain of laminin 5 (LAMB3) and subsequent analysis by agarose gel electrophoresis showed a more slowly migrating band in the affected fetus compared with the normal control. Nucleotide sequencing of the abnormal PCR product revealed a homozygous 77 bp duplication within the exon, resulting in a premature termination codon 250 bp downstream from the 3' end of the duplication. Maternal DNA was heterozygous for the mutant and wild-type alleles. These findings illustrate the genetic basis of the skin disease in this case and also offer the prospects of a simple, rapid, and reliable first-trimester DNA-based prenatal, or even preimplantation, diagnostic test for future pregnancies in this family.