title: Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa.
abstract: Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a clinically and genetically heterogeneous group of recessively inherited blistering disease of skin and mucous membranes. In this report, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The paternally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA decay. The maternally inherited mutation is a G-->A transition at the last base of exon 7 (628G-->A) which converts a codon for glutamic acid in a codon for lysine (E210K). The mutation 628G-->A alters the correct splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addition to the RNA transcript carrying the G-->A substitution. This result is compatible with the reduced expression of mutated laminin 5 molecules with altered biological activity, and the mild JEB phenotype observed in the patient.
authors.affiliation: Laboratory of Molecular & Cell Biology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Posteraro
authors.forename: S
authors.initials: S
authors.lastname: Sorvillo
authors.forename: L
authors.initials: L
authors.lastname: Gagnoux-Palacios
authors.forename: C
authors.initials: C
authors.lastname: Angelo
authors.forename: M
authors.initials: M
authors.lastname: Paradisi
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
authors.forename: D
authors.initials: D
authors.lastname: Castiglia
authors.forename: G
authors.initials: G
authors.lastname: Zambruno
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002675:Child, Preschool; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D012322:RNA Precursors; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase; D000097794:Kalinin