Ja. Mcgrath et al., GENETIC-BASIS OF LETHAL JUNCTIONAL EPIDERMOLYSIS-BULLOSA IN AN AFFECTED FETUS - IMPLICATIONS FOR PRENATAL-DIAGNOSIS IN ONE FAMILY, Prenatal diagnosis, 15(7), 1995, pp. 647-654
Fetal skin biopsy at 20 weeks' gestation in a woman at risk for a chil
d with the lethal skin-blistering disorder junctional epidermolysis bu
llosa (Herlitz) confirmed an affected fetus. Genomic DNA from the abor
ted fetus was examined for mutations in laminin 5, a macromolecule inv
olved in adhesion at the dermal-epidermal junction, and a candidate pr
otein 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 affecte
d fetus compared with the normal control. Nucleotide sequencing of the
abnormal PCR product revealed a homozygous 77 bp duplication within t
he 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 geneti
c basis of the skin disease in this case and also offer the prospects
of a simple, rapid, and reliable first-trimester DNA-based prenatal, o
r even preimplantation, diagnostic test for future pregnancies in this
family.