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.
Department of Dermatology, Thomas Jefferson University, Philadelphia, PA, USA.
J A
JA
McGrath
J R
JR
McMillan
M G
MG
Dunnill
L
L
Pulkkinen
A M
AM
Christiano
C H
CH
Rodeck
R A
RA
Eady
J
J
Uitto
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001706:Biopsy; D004247:DNA / Q000032:analysis* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D016109:Epidermolysis Bullosa, Junctional / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007797:Laminin / Q000235:genetics; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012867:Skin / Q000737:chemistry / Q000196:embryology / Q000473:pathology
D007797:Laminin; D004247:DNA