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

Abstract

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 β3 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.