Cloning of the laminin alpha 3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa.
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.
Vidal
F
F
U385 INSERM, Faculté de Médecine, Nice, France.
Baudoin
C
C
Miquel
C
C
Galliano
M F
MF
Christiano
A M
AM
Uitto
J
J
Ortonne
J P
JP
Meneguzzi
G
G
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
D015815:Cell Adhesion Molecules; D018388:Codon, Terminator; D018076:DNA, Complementary; D007797:Laminin; D000097794:Kalinin; C095567:laminin alpha 3