Type XVII collagen gene mutations in XXXX and prospects for gene therapy.

@entity1 @entity1665 @entity5858 @entity2318 @entity5806 @entity3202 @entity272 @entity74 @entity2193
Non-Herlitz @entity3202 (nH-JEB) is caused predominantly by mutations leading to premature stop codons on both alleles of the type XVII collagen gene ( @entity5858 ). The analysis of mutations in this gene has provided a means of correlating genotype with phenotype of nH-JEB @entity1 . The phenotype of nH-JEB is characterized by generalized blistering of skin and mucous membranes with @entity2318 and @entity5806 . @entity1665 is a distinct feature of nH-JEB @entity1 , but one that is not associated with the severity of the disease at other sites. @entity2193 and pitting of the teeth are also characteristic for nH-JEB and can be used to facilitate the correct diagnosis in @entity1 with a blistering @entity272 . Analysis of the biological consequences of mutations in the @entity5858 gene has shown that most @entity1 lack type XVII collagen mRNA due to nonsense-mediated mRNA decay. @entity1 with these mutations can therefore be a target for corrective gene therapy using vectors coding for full-length type XVII collagen. Proof of principle for this approach has recently been demonstrated. The analysis of naturally occurring phenomena of gene correction in the @entity5858 gene provides evidence for other mechanisms of gene correction in @entity74 . For example, exclusion of an exon carrying a mutation can lead to a milder phenotype of nH-JEB than predicted by the original mutation. In addition, we have gained data suggesting that @entity5858 exons harbouring pathogenic mutations can also be repaired by trans-splicing, i.e. aligning corrected RNA sequences to introns in the vicinity of faulty exons in the @entity5858 premtRNA.
