Novel and recurrent COL7A1 mutations in Chilean patients with dystrophic epidermolysis bullosa

Rodrı́guez, Fernando; Gana, María José; Yubero, María Joao; Zillmann, Gisela; Krämer, Susanne; Catalán, Javiera; Rubio-Astudillo, Julia; González, Sergio; Liu, Lu; Ozoemena, Linda; Mellerio, J.; McGrath, John A.; Palisson, Francis; Conget, Paulette

doi:10.1016/j.jdermsci.2011.11.010

Cited by 17 publications

(17 citation statements)

References 14 publications

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“…Our study is the first to investigate the molecular epidemiology of patients with JEB in South America, and is comparable only with a report on Chilean patients with dystrophic EB . These results are extremely relevant for patients with EB in Chile and can be immediately used in clinic to improve patient care and prognosis.…”

Section: Overview Of the 23 Chilean Patients With Junctional Epidermosupporting

confidence: 75%

Molecular epidemiology of junctional epidermolysis bullosa: discovery of novel and frequent LAMB3 mutations in Chilean patients with diagnostic significance

et al. 2017

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Section: Overview Of the 23 Chilean Patients With Junctional Epidermosupporting

confidence: 75%

Molecular epidemiology of junctional epidermolysis bullosa: discovery of novel and frequent LAMB3 mutations in Chilean patients with diagnostic significance

et al. 2017

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“…We have previously suggested a founder effect for c.6527insC as Spanish patients carrying this mutation share an intragenic ancestral haplotype (H5) of approximately 30 kb, which is present at a low frequency in the general, ethnically matched population 3,4 . In agreement, the c.6527insC mutation recurrence has also been recently disclosed in the RDEB population in Chile where waves of Spanish migration occurred at different historical periods 5 . Notably, this mutation has also been found in isolated patients from France 6 and Germany, 7 two countries with a long history of mid‐20th century Spanish immigration.…”

supporting

confidence: 59%

Recessive dystrophic epidermolysis bullosa: the origin of the c.6527insC mutation in the Spanish population

Sánchez-Jimeno

Cuadrado-Corrales

Aller

et al. 2012

British Journal of Dermatology

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“…This is the case of c.6527insC at E80, which is characteristic of the Spanish and some Latin American RDEB cohorts. 14 , 24 To our knowledge, this is the most prevalent COL7A1 mutation. Thus, an advanced gene-editing strategy tailored to this mutation would be beneficial for a large patient cohort.…”

Section: Discussionmentioning

confidence: 94%

Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing

et al. 2019

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Gene editing constitutes a novel approach for precisely correcting disease-causing gene mutations. Frameshift mutations in COL7A1 causing recessive dystrophic epidermolysis bullosa are amenable to open reading frame restoration by non-homologous end joining repair-based approaches. Efficient targeted deletion of faulty COL7A1 exons in polyclonal patient keratinocytes would enable the translation of this therapeutic strategy to the clinic. In this study, using a dual single-guide RNA (sgRNA)-guided Cas9 nuclease delivered as a ribonucleoprotein complex through electroporation, we have achieved very efficient targeted deletion of COL7A1 exon 80 in recessive dystrophic epidermolysis bullosa (RDEB) patient keratinocytes carrying a highly prevalent frameshift mutation. This ex vivo non-viral approach rendered a large proportion of corrected cells producing a functional collagen VII variant. The effective targeting of the epidermal stem cell population enabled long-term regeneration of a properly adhesive skin upon grafting onto immunodeficient mice. A safety assessment by next-generation sequencing (NGS) analysis of potential off-target sites did not reveal any unintended nuclease activity. Our strategy could potentially be extended to a large number of COL7A1 mutation-bearing exons within the long collagenous domain of this gene, opening the way to precision medicine for RDEB.

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Novel and recurrent COL7A1 mutations in Chilean patients with dystrophic epidermolysis bullosa

Cited by 17 publications

References 14 publications

Molecular epidemiology of junctional epidermolysis bullosa: discovery of novel and frequent LAMB3 mutations in Chilean patients with diagnostic significance

Molecular epidemiology of junctional epidermolysis bullosa: discovery of novel and frequent LAMB3 mutations in Chilean patients with diagnostic significance

Recessive dystrophic epidermolysis bullosa: the origin of the c.6527insC mutation in the Spanish population

Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing

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