Human molecular genetics

Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia.

PMID 9158140


Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. For this purpose, we first determined the genomic organization of ITGA6, and placed the gene on chromosome 2q by high resolution radiation hybrid mapping. Heteroduplex analysis of PCR products containing the individual exons of ITGA6, followed by direct nucleotide sequencing, revealed that the proband was homozygous for a G-to-T transversion in the +1 position of intron 12. This mutation, 1856+1G-->T, affects an invariant base of the 5' donor splice site predicting aberrant splicing involving exon 12. The mutation was verified in the proband's DNA by restriction enzyme digestion which also confirmed that the parents were heterozygous carriers of this mutation. Altered expression of alpha6 integrin, which forms a heterodimer with the beta4 subunit at the dermal-epidermal junction, would explain fragility and blistering as a result of minor trauma to the skin.