title: Laminin 5 genes and Herlitz junctional epidermolysis bullosa: novel mutations and polymorphisms in the LAMB3 and LAMC2 genes. Mutations in brief no. 190. Online.
abstract: Herlitz junctional epidermolysis bullosa (H-JEB; OMIM #226700) is a lethal, autosomal recessive blistering disorder characterized by fragility of the skin and other specialized epithelia. Previously, mutations in the laminin 5 genes (LAMA3, LAMB3, and LAMC2) have been disclosed, most of them in LAMB3. In this study, we have examined the genetic basis of H-JEB in three families utilizing heteroduplex analysis and automated nucleotide sequencing. In one family, the proband was compound heterozygote for previously unpublished LAMB3 mutations, 1482delC and W95X. In two other families, the probands were found to be homozygous for novel nonsense mutations C553X and K822X in the LAMC2 gene. These mutations result in premature termination codons and predict truncation of the corresponding polypeptides. Also, during the search of laminin 5 mutations, 18 LAMB3 and LAMC2 polymorphisms were discovered, 9 of them being previously undescribed. Delineation of novel homozygous nonsense mutations in the LAMB3 and LAMC2 genes, with previous demonstrations of LAMA3 mutations, re-emphasizes the concept that stop codon mutations in both alleles of any of the three laminin 5 genes result in the severe H-JEB phenotype.
authors.affiliation: Department of Dermatology, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Philadelphia 19107, PA. USA.
authors.forename: A
authors.initials: A
authors.lastname: Kon
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Tamai
authors.forename: H
authors.initials: H
authors.lastname: Tagami
authors.forename: I
authors.initials: I
authors.lastname: Hashimoto
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics*; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D000097794:Kalinin