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Cutaneous mosaicism: right before our eyes

Published on May 1, 2007in Journal of Clinical Investigation12.282
· DOI :10.1172/JCI32111
Jorge Frank18
Estimated H-index: 18
,
Rudolf Happle55
Estimated H-index: 55
Abstract
Autosomal recessive cutaneous disorders, including various types of epidermolysis bullosa (EB), usually manifest shortly after birth. The clinical course of these diseases is often characterized by severe complications, limited therapeutic options, and a poor prognosis. A study by Pasmooij et al. reported in this issue of the JCI unravels the molecular mechanisms by which germline mutations in non-Herlitz junctional EB can be corrected in vivo by multiple spontaneously occurring somatic mutational events, a phenomenon known as revertant mosaicism (see the related article beginning on page 1240). These insights open new avenues of thinking for the design of future gene therapy strategies for skin diseases.
  • References (26)
  • Citations (22)
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References26
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#2Hendri H. PasH-Index: 31
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Revertant mosaicism due to in vivo reversion of an inherited mutation has been described in the genetic skin disease epidermolysis bullosa (EB) for the genes KRT14 and COL17A1. Here we demonstrate the presence of multiple second-site mutations, all correcting the germline mutation LAMB3:c.628G→A;p.E210K, in 2 unrelated non-Herlitz junctional EB patients with revertant mosaicism. Both probands had a severe reduction in laminin-332 expression in their affected skin. Remarkably, the skin on the low...
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Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells
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Many patients with tyrosinaemia type 1 have a mosaic pattern of fumarylacetoacetase (FAH) immunopositive or immunonegative nodules in liver tissue. This phenomenon has been explained by a spontaneous reversion of the mutation in one allele to a normal genotype, but only a few nodules have been examined. We now report on a Norwegian patient, compound heterozygous for the mutations IVS12g+5→a and G1009→A, with liver mosaicism, but with an immunopositive nodule in which both primary mutations were ...
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This chapter traverses contemporary understandings of the genetic architecture of human disease, and explores the clinical implications of the current state of knowledge. Many different classes of genetic mutations have been implicated as being involved in predisposition to certain diseases, and researchers are continually uncovering other means by which genetics plays an important role in human disease, such as with somatic genetic mosaicism. Putative “de novo” mutations can represent cases of ...
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