Human Molecular Genetics, Vol 6, 669-674, Copyright © 1997 by Oxford University Press
L Pulkkinen, VE Kimonis, Y Xu, EN Spanou, WH McLean and J Uitto
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.
ARTICLES
Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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