Junctional epidermolysis bullosa gravis (Herlitz): diagnostic and genetic aspects

We report on a boy suffering from lethal junctional epidermolysis bullosa g ravis (JEBH) (Herlitz-type) (OMIM 226700). Screening for mutations of LAMB3 gene with polymerase chain reaction (PCR) amplification of all exons from genomic DNA and subsequent heteroduplex analysis and dideoxynucleotide sequ encing of heteroduplex forming PCR products disclosed two mutations: the re current maternal mutation R635X and the novel paternal mutation 1629insG, b oth in exon 14 of LAMB3. Both mutations lead to a premature termination cod e, non-sense mediated mRNA decay and to absence of the synthesis of the bet a3 chain of laminin 5. During the mutation screening of the index patient a second pregnancy was ascertained. After amniocentesis (14 + 1 week of preg nancy), prenatal diagnosis from fetal cells was performed and compound hete rozygosity for both mutations was evident. The consultants decided to have a termination of pregnancy shortly after the diagnosis. Remarkable skin fra gility of the fetus was evident by clinical examination. Complete absence o f laminin 5 could be demonstrated by immunofluorescence staining. By the th ird pregnancy of this couple so far screened for mutations by chorionic vil lus sampling for prenatal molecular diagnosis a healthy but heterozygous ch ild is expected.