title: Compound heterozygosity for nonsense and missense mutations in the LAMB3 gene in nonlethal junctional epidermolysis bullosa.
abstract: Mutations in the genes encoding laminin 5 (LAMA3, LAMB3, and LAMC2) have been delineated in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa, particularly in the lethal (Herlitz) variant. In this study, we searched for mutations in these genes in two patients with nonlethal forms of junctional epidermolysis bullosa using polymerase chain reaction amplification of genomic DNA, followed by heteroduplex analysis and direct automated nucleotide sequencing. Both patients were found to be compound heterozygotes for the same nonsense mutation on one LAMB3 allele, and different missense mutations on the other LAMB3 allele. The combination of nonsense and a missense mutation in the LAMB3 gene appears to be important in determining the milder clinical phenotype in some cases of the nonlethal forms of junctional epidermolysis bullosa involving abnormalities in laminin 5.
authors.affiliation: Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D007797:Laminin