title: Identification of a homozygous exon-skipping mutation in the LAMC2 gene in a patient with Herlitz's junctional epidermolysis bullosa.
abstract: We describe a family with the Herlitz type of junctional epidermolysis bullosa, in which the disease is associated with a homozygous splice-site mutation in the gamma 2-chain gene (LAMC2) of laminin-5. The mutation consists of a G-to-T substitution resulting in the out-of-frame skipping of exon 7, a frame shift, and premature stop codon accompanied by a severe reduction in the level of mRNA from the mutant allele. The distribution of the wild-type and mutated gamma 2-chain alleles in family members implicates the mutation in the pathology and confirms the haplotypes of the healthy carriers previously determined by genetic linkage analysis. Our results confirm that the lethal Herlitz junctional epidermolysis bullosa phenotype is caused by mutations resulting in an altered synthesis of laminin-5.
authors.affiliation: INSERM U385, Faculté de Médicine, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Vailly
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: J P
authors.initials: JP
authors.lastname: Ortonne
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
mesh_terms: D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D000097794:Kalinin