title: A homozygous nonsense mutation in the beta 3 chain gene of laminin 5 (LAMB3) in Herlitz junctional epidermolysis bullosa.
abstract: Herlitz junctional epidermolysis bullosa (H-JEB) is a severe autosomal recessive disorder characterized by blister formation within the dermal-epidermal basement membrane. Based on immunofluorescence analysis recognizing laminin 5 epitopes (previously known as nicein/kalinin), the genes for this lamina lucida protein have been proposed as candidate genes in H-JEB. In this study, we examined the gene encoding the beta 3 polypeptide chain of laminin 5 (LAMB3) by Northern hybridization and RT-PCR analysis of keratinocyte mRNA from a proband in a family with H-JEB. Northern analysis revealed markedly reduced levels of the laminin beta 3 chain mRNA. Amplification of mRNA by RT-PCR, followed by direct nucleotide sequencing, revealed a homozygous C-to-T transition resulting in a premature termination codon (CGA --> TGA) on both alleles. This mutation was verified at the genomic DNA level, and both parents were shown to be heterozygous carriers of the same mutation. This is the first description of a mutation in the laminin beta 3 chain gene (LAMB3) of laminin 5 in an H-JEB patient.
authors.affiliation: Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: D
authors.initials: D
authors.lastname: Gerecke
authors.forename: D W
authors.initials: DW
authors.lastname: Wagman
authors.forename: R E
authors.initials: RE
authors.lastname: Burgeson
authors.forename: M R
authors.initials: MR
authors.lastname: Pittelkow
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007797:Laminin / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D007797:Laminin; D012333:RNA, Messenger