RT Journal Article
T1 Revertant mosaicism due to second-site mutation in COL7A1 in patient with recessive dystrophic epidermolysis bullosa
A1 Pasmooij, Anna M. G.
A1 García Díez, Marta
A1 Escámez Toledano, María José
A1 Nijenhuis, A. Miranda
A1 Azon, Antoni
A1 Cuadrado-Corrales, Natividad
A1 Jonkman, Marcel F.
A1 Río Nechaevsky, Marcela del
AB Despite the high incidence of revertant mosaicism (35%) in patients with the genetic skin disease epidermolysis bullosa (EB) due to correcting mutations in the genes COL17A1 and LAMB3, revertant mosaicism has not been described for COL7A1 until recently. Mutations in COL7A1 are responsible for the most devastating form of EB in adults, which is characterized by cocooned “mitten” deformities of the hands. This report shows in vivo reversion of an inherited COL7A1 mutation in a patient with recessive dystrophic EB who was homozygous for the frameshift mutation COL7A1:c.6527insC,p.2176FsX337. The patient exhibited a patch of clinically healthy revertant skin on her left forearm. The second-site mutation c.6528delT, which is present in revertant keratinocytes, resulted in correction of the reading frame. As the new CCC codon codes for the same amino acid proline as the wild-type codon CCT, the revertant cells expressed wild-type type VII collagen polypeptide, leading to restoration of skin function. We hypothesize that, on careful examination, revertant mosaicism might be found to be more common in patients with type VII collagen-deficient EB. Furthermore, the revertant keratinocytes might offer the possibility to explore cell-based therapeutic strategies, by culturing in vitro and subsequently grafting as part of bioengineered dermo-epidermal substitutes on affected skin.
PB Elsevier
SN 0022-202X
YR 2010
FD 2010-10
LK https://hdl.handle.net/10016/33519
UL https://hdl.handle.net/10016/33519
LA eng
NO This work was supported by the Dutch Butterfly Child Foundation in the Netherlands, by INTRA/08/714.1 from CIBERER, and by SAF2007-61019 from MICINN in Spain.
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RD 19 may. 2024