Herlitz Junctional Epidermolysis Bullosa: Novel and Recurrent Mutations in the LAMB3 Gene and the Population Carrier Frequency

SummaryHerlitz junctional epidermolysis bullosa is a heritable bullous disease caused by mutations found primarily in the β3 chain of laminin 5 (LAMB3). In this study, we examined the LAMB3 gene for mutations in 22 Herlitz junctional epidermolysis bullosa families, and identified 15 distinct mutations, eight of them previously unreported, bringing the total number of distinct Herlitz junctional epidermolysis bullosa mutations in LAMB3 to 35. Examination of the mutation database revealed several recurrent mutations that have been reported, as well as six previously unreported. All recurrent mutations may be readily detected by polymerase chain reaction of genomic DNA and restriction endonuclease digestion. Mutation screening and prenatal diagnosis of families at risk may be expedited by molecular testing for these recurrent mutations prior to screening the entire gene. Finally, the U.S. population carrier risk for Herlitz junctional epidermolysis bullosa and all variants of junctional epidermolysis bullosa was calculated to be one in 781 and one in 350, respectively, while the overall epidermolysis bullosa carrier frequency was calculated to be one in 113. These data allow accurate testing, counseling, and risk calculation for nuclear families, as well as extended family members at risk for junctional epidermolysis bullosa