Publication

Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa

Bremer, J., van der Heijden, E. H., Eichhorn, D. S., Meijer, R., Lemmink, H. H., Scheffer, H., Sinke, R. J., Jonkman, M. F., Pasmooij, A. M. G. & Van den Akker, P. C., 18-Dec-2019, In : Molecular therapy - Nucleic acids. 18, p. 465-475 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Bremer, J., van der Heijden, E. H., Eichhorn, D. S., Meijer, R., Lemmink, H. H., Scheffer, H., Sinke, R. J., Jonkman, M. F., Pasmooij, A. M. G., & Van den Akker, P. C. (2019). Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa. Molecular therapy - Nucleic acids, 18, 465-475. https://doi.org/10.1016/j.omtn.2019.09.009

Author

Bremer, Jeroen ; van der Heijden, Elisabeth H ; Eichhorn, Daryll S ; Meijer, Rowdy ; Lemmink, Henny H ; Scheffer, Hans ; Sinke, Richard J ; Jonkman, Marcel F ; Pasmooij, Anna M G ; Van den Akker, Peter C. / Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa. In: Molecular therapy - Nucleic acids. 2019 ; Vol. 18. pp. 465-475.

Harvard

Bremer, J, van der Heijden, EH, Eichhorn, DS, Meijer, R, Lemmink, HH, Scheffer, H, Sinke, RJ, Jonkman, MF, Pasmooij, AMG & Van den Akker, PC 2019, 'Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa', Molecular therapy - Nucleic acids, vol. 18, pp. 465-475. https://doi.org/10.1016/j.omtn.2019.09.009

Standard

Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa. / Bremer, Jeroen; van der Heijden, Elisabeth H; Eichhorn, Daryll S; Meijer, Rowdy; Lemmink, Henny H; Scheffer, Hans; Sinke, Richard J; Jonkman, Marcel F; Pasmooij, Anna M G; Van den Akker, Peter C.

In: Molecular therapy - Nucleic acids, Vol. 18, 18.12.2019, p. 465-475.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Bremer J, van der Heijden EH, Eichhorn DS, Meijer R, Lemmink HH, Scheffer H et al. Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa. Molecular therapy - Nucleic acids. 2019 Dec 18;18:465-475. https://doi.org/10.1016/j.omtn.2019.09.009


BibTeX

@article{18bc560f980b444a9bfeb2fce69ad804,
title = "Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa",
abstract = "Dystrophic epidermolysis bullosa (DEB) is a devastating blistering disease affecting skin and mucous membranes. It is caused by pathogenic variants in the COL7A1 gene encoding type VII collagen, and can be inherited dominantly or recessively. Recently, promising proof-of-principle has been shown for antisense oligonucleotide (AON)-mediated exon skipping as a therapeutic approach for DEB. However, the precise phenotypic effect to be anticipated from exon skipping, and which patient groups could benefit, is not yet clear. To answer these questions, we studied new clinical and molecular data on seven patients from the Dutch EB registry and reviewed the literature on COL7A1 exon skipping variants. We found that phenotypes associated with dominant exon skipping cannot be distinguished from phenotypes caused by other dominant DEB variants. Recessive exon skipping phenotypes are generally relatively mild in the spectrum of recessive DEB. Therefore, for dominant DEB, AON-mediated exon skipping is unlikely to ameliorate the phenotype. In contrast, the overall severity of phenotypes associated with recessive natural exon skipping pivots toward the milder end of the spectrum. Consequently, we anticipate AON-mediated exon skipping for recessive DEB caused by bi-allelic null variants should lead to a clinically relevant improvement of this devastating phenotype.",
author = "Jeroen Bremer and {van der Heijden}, {Elisabeth H} and Eichhorn, {Daryll S} and Rowdy Meijer and Lemmink, {Henny H} and Hans Scheffer and Sinke, {Richard J} and Jonkman, {Marcel F} and Pasmooij, {Anna M G} and {Van den Akker}, {Peter C}",
note = "Copyright {\textcopyright} 2019 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = dec,
day = "18",
doi = "10.1016/j.omtn.2019.09.009",
language = "English",
volume = "18",
pages = "465--475",
journal = "Molecular therapy - Nucleic acids",
issn = "2162-2531",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa

AU - Bremer, Jeroen

AU - van der Heijden, Elisabeth H

AU - Eichhorn, Daryll S

AU - Meijer, Rowdy

AU - Lemmink, Henny H

AU - Scheffer, Hans

AU - Sinke, Richard J

AU - Jonkman, Marcel F

AU - Pasmooij, Anna M G

AU - Van den Akker, Peter C

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2019/12/18

Y1 - 2019/12/18

N2 - Dystrophic epidermolysis bullosa (DEB) is a devastating blistering disease affecting skin and mucous membranes. It is caused by pathogenic variants in the COL7A1 gene encoding type VII collagen, and can be inherited dominantly or recessively. Recently, promising proof-of-principle has been shown for antisense oligonucleotide (AON)-mediated exon skipping as a therapeutic approach for DEB. However, the precise phenotypic effect to be anticipated from exon skipping, and which patient groups could benefit, is not yet clear. To answer these questions, we studied new clinical and molecular data on seven patients from the Dutch EB registry and reviewed the literature on COL7A1 exon skipping variants. We found that phenotypes associated with dominant exon skipping cannot be distinguished from phenotypes caused by other dominant DEB variants. Recessive exon skipping phenotypes are generally relatively mild in the spectrum of recessive DEB. Therefore, for dominant DEB, AON-mediated exon skipping is unlikely to ameliorate the phenotype. In contrast, the overall severity of phenotypes associated with recessive natural exon skipping pivots toward the milder end of the spectrum. Consequently, we anticipate AON-mediated exon skipping for recessive DEB caused by bi-allelic null variants should lead to a clinically relevant improvement of this devastating phenotype.

AB - Dystrophic epidermolysis bullosa (DEB) is a devastating blistering disease affecting skin and mucous membranes. It is caused by pathogenic variants in the COL7A1 gene encoding type VII collagen, and can be inherited dominantly or recessively. Recently, promising proof-of-principle has been shown for antisense oligonucleotide (AON)-mediated exon skipping as a therapeutic approach for DEB. However, the precise phenotypic effect to be anticipated from exon skipping, and which patient groups could benefit, is not yet clear. To answer these questions, we studied new clinical and molecular data on seven patients from the Dutch EB registry and reviewed the literature on COL7A1 exon skipping variants. We found that phenotypes associated with dominant exon skipping cannot be distinguished from phenotypes caused by other dominant DEB variants. Recessive exon skipping phenotypes are generally relatively mild in the spectrum of recessive DEB. Therefore, for dominant DEB, AON-mediated exon skipping is unlikely to ameliorate the phenotype. In contrast, the overall severity of phenotypes associated with recessive natural exon skipping pivots toward the milder end of the spectrum. Consequently, we anticipate AON-mediated exon skipping for recessive DEB caused by bi-allelic null variants should lead to a clinically relevant improvement of this devastating phenotype.

U2 - 10.1016/j.omtn.2019.09.009

DO - 10.1016/j.omtn.2019.09.009

M3 - Article

C2 - 31670143

VL - 18

SP - 465

EP - 475

JO - Molecular therapy - Nucleic acids

JF - Molecular therapy - Nucleic acids

SN - 2162-2531

ER -

ID: 101544215