UNASSIGNED: Mutations in the @entity5858 gene lead to the genetic blistering disorder @entity3202 generalized intermediate (JEB-gen intermed). Antisense oligonucleotides (AON)-mediated exon skipping is a strategy that aims to skip the mutation-containing exon, and thereby produce a smaller, although functional protein. @entity5858 is an interesting candidate, as 53 out of the 55 can be skipped without disturbing the reading frame (96%). Information on the functionality of the shortened protein product is important to obtain support for this therapeutic strategy. Here we report a @entity1 with JEB-gen intermed with amelioration of the phenotype due to exon 49 skipping by two distinct mechanisms, premature termination codon-induced exon skipping and revertant mosaicism, which both induced skipping of the same exon. The @entity1 was compound heterozygous for two inherited @entity5858 mutations, a frame-shift mutation in exon 18 ( @entity69347 , @entity69348 ) and a nonsense mutation in exon 49 ( @entity69349 , @entity69350 ). Upon clinical examination skin patches were found that were resistant to blister formation. In these patches naturally corrected cells were present that harboured an additional splice-site mutation @entity69351 resulting in skipping of the mutation-containing exon 49. This natural gene therapy phenomenon shows that residues 1140-1169-deleted type XVII collagen is largely functional. In addition, in affected skin cells a low level of exon 49 skipping was observed. In conclusion, our results support the notion that skipping of a mutated in-frame exon in @entity5858 ameliorates the phenotype. This article is protected by copyright. All rights reserved.

Amelioration of XXXX due to exon skipping.

@entity1 :: ('9606', 'Species') :: ['patient'] @entity69348 :: ('p|FS|A|497|V|23', 'ProteinMutation') :: ['p.Ala497Valfs*23'] @entity5858 :: ('1308', 'Gene') :: ['COL17A1'] @entity69351 :: ('c|SUB|G|3419-1|T', 'DNAMutation') :: ['c.3419-1G>T'] @entity69347 :: ('c|INDEL|1490_1491|T', 'DNAMutation') :: ['c.1490_1491delinsT'] @entity69349 :: ('c|SUB|G|3487|T', 'DNAMutation') :: ['c.3487G>T'] @entity69350 :: ('p|SUB|E|1163|X', 'ProteinMutation') :: ['p.Glu1163Ter'] @entity3202 :: ('MESH:D016109', 'Disease') :: ['junctional epidermolysis bullosa']
@entity3202 :: (MESH:D016109,Disease) :: ['junctional epidermolysis bullosa']
