title: Cloning of the laminin alpha 3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa.
abstract: Laminin 5 and laminin 6 are basement membrane proteins synthesized by the basal cells of stratifying squamous epithelia. Altered expression of laminin 5 has been associated with Herlitz junctional epidermolysis bullosa (H-JEB), a severe epidermal blistering disorder inherited as an autosomal recessive disease. We have isolated cDNA clones encoding the alpha 3 chain of laminin 5 and searched for mutations in the LAMA3 gene in H-JEB patients. In one H-JEB family, an affected individual exhibited drastically reduced immunoreactivity to antibodies directed against the alpha 3 chain of laminin 5 and an impaired expression of the corresponding mRNA transcripts. RT-PCR analysis of mRNA extracted from the proband's keratinocytes identified a homozygous single basepair deletion in the transcripts encoding the laminin alpha 3A and alpha 3B isoforms. The mutation causes a frameshift and premature termination codon in both alleles of the LAMA3 gene. Inheritance of the clinical H-JEB phenotype was consistent with the segregation of the mutated allele in the family. We also report the identity of the alpha chains of laminin 5 and epiligrin and provide evidence that LAMA3 transcripts are distinct from the laminin 6 alpha chain mRNA.
authors.affiliation: U385 INSERM, Faculté de Médecine, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Vidal
authors.forename: C
authors.initials: C
authors.lastname: Baudoin
authors.forename: C
authors.initials: C
authors.lastname: Miquel
authors.forename: M F
authors.initials: MF
authors.lastname: Galliano
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
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: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018388:Codon, Terminator; D018076:DNA, Complementary; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000276:immunology; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D007797:Laminin / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D017384:Sequence Deletion; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D018388:Codon, Terminator; D018076:DNA, Complementary; D007797:Laminin; D000097794:Kalinin; C095567:laminin alpha 3