Novel and very rare causative variants in the COL7A1 gene of Vietnamese patients with recessive dystrophic epidermolysis bullosa revealed by whole‐exome sequencing

Dystrophic epidermolysis bullosa (DEB) is a rare form of genodermatosis characterized by skin blisters, milia, scarring over the entire body, and nail dystrophy. In this study, a pedigree with one affected member with skin blisters, and a clinical diagnosis of epidermolysis bullosa who was a result of a non-consanguineous marriage, was investigated by whole-exome sequencing (WES). This survey revealed that the proband is a compound heterozygote for a previously reported heterozygous missense variant (c.6205C>T) and a heterozygous deletion of exons 13–24 in the COL7A1 gene. This study indicates that the use of WES along with copy number variation (CNV) analysis gives a higher diagnostic yield for such patients. Moreover, considering the autosomal recessive and dominant forms of the disease, both caused by variants in one gene, proper interpretation and classification of novel variants in heterozygous as well as homozygous states is always a major challenge.

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Utility of whole-exome sequencing in detecting novel compound heterozygous mutations inCOL7A1among families with severe recessive dystrophic epidermolysis bullosa in India - implications on diagnosis, prognosis and prenatal testing

Journal of the European Academy of Dermatology and Venereology ◽

10.1111/jdv.14909 ◽

2018 ◽

Vol 32 (12) ◽

pp. e433-e435 ◽

Cited By ~ 3

Author(s):

R. Mahajan ◽

S.K. Vellarikkal ◽

S. Handa ◽

A. Verma ◽

R. Jayarajan ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Epidermolysis Bullosa ◽

Prenatal Testing ◽

Compound Heterozygous ◽

Dystrophic Epidermolysis Bullosa ◽

Whole Exome ◽

Recessive Dystrophic Epidermolysis Bullosa ◽

Compound Heterozygous Mutations

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Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa

F1000Research ◽

10.12688/f1000research.8380.2 ◽

2016 ◽

Vol 5 ◽

pp. 900 ◽

Cited By ~ 1

Author(s):

Shamsudheen Karuthedath Vellarikkal ◽

Rijith Jayarajan ◽

Ankit Verma ◽

Sreelata Nair ◽

Rowmika Ravi ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Epidermolysis Bullosa ◽

Sporadic Case ◽

The Body ◽

Epidermolysis Bullosa Simplex ◽

Dominant Form ◽

Dystrophic Epidermolysis Bullosa ◽

Frameshift Deletion ◽

Whole Exome

Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB) is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

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Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa

F1000Research ◽

10.12688/f1000research.8380.1 ◽

2016 ◽

Vol 5 ◽

pp. 900 ◽

Cited By ~ 1

Author(s):

Shamsudheen Karuthedath Vellarikkal ◽

Rijith Jayarajan ◽

Ankit Verma ◽

Sreelata Nair ◽

Rowmika Ravi ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Epidermolysis Bullosa ◽

Sporadic Case ◽

The Body ◽

Epidermolysis Bullosa Simplex ◽

Dominant Form ◽

Dystrophic Epidermolysis Bullosa ◽

Frameshift Deletion ◽

Whole Exome

Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB) is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

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Compound Heterozygosity for a Recessive Glycine Substitution and a Splice Site Mutation in the COL7A1 Gene Causes an Unusually Mild Form of Localized Recessive Dystrophic Epidermolysis Bullosa

Journal of Investigative Dermatology ◽

10.1046/j.1523-1747.1998.00397.x ◽

1998 ◽

Vol 111 (5) ◽

pp. 744-750 ◽

Cited By ~ 30

Author(s):

Michela Terracina ◽

Patrizia Posteraro ◽

Giovanna Zambruno ◽

Daniele Castiglia ◽

Margit Schubert ◽

...

Keyword(s):

Splice Site ◽

Epidermolysis Bullosa ◽

Splice Site Mutation ◽

Compound Heterozygosity ◽

Mild Form ◽

Site Mutation ◽

Dystrophic Epidermolysis Bullosa ◽

Recessive Dystrophic Epidermolysis Bullosa ◽

Glycine Substitution ◽

Col7a1 Gene

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Development of Minicircle Vectors Encoding COL7A1 Gene with Human Promoters for Non-Viral Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

International Journal of Molecular Sciences ◽

10.3390/ijms222312774 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12774

Author(s):

Xianqing Wang ◽

Fatma Alshehri ◽

Darío Manzanares ◽

Yinghao Li ◽

Zhonglei He ◽

...

Keyword(s):

Epidermolysis Bullosa ◽

Gene Replacement ◽

Epidermal Keratinocytes ◽

Viral Gene ◽

Cmv Promoter ◽

Human Epidermal Keratinocytes ◽

Dystrophic Epidermolysis Bullosa ◽

Type Vii Collagen ◽

Recessive Dystrophic Epidermolysis Bullosa ◽

Col7a1 Gene

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare autosomal inherited skin disorder caused by mutations in the COL7A1 gene that encodes type VII collagen (C7). The development of an efficient gene replacement strategy for RDEB is mainly hindered by the lack of vectors able to encapsulate and transfect the large cDNA size of this gene. To address this problem, our group has opted to use polymeric-based non-viral delivery systems and minicircle DNA. With this approach, safety is improved by avoiding the usage of viruses, the absence of bacterial backbone, and the replacement of the control viral cytomegalovirus (CMV) promoter of the gene with human promoters. All the promoters showed impressive C7 expression in RDEB skin cells, with eukaryotic translation elongation factor 1 α (EF1α) promoter producing higher C7 expression levels than CMV following minicircle induction, and COL7A1 tissue-specific promoter (C7P) generating C7 levels similar to normal human epidermal keratinocytes. The improved system developed here has a high potential for use as a non-viral topical treatment to restore C7 in RDEB patients efficiently and safely, and to be adapted to other genetic conditions.

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