Splicing mutation in the <i>COL7A1</i> gene mRNA exon 71 in a female patient with pretibial epidermolysis bullosa

Kitazawa, Takio; Kawakami, Tamihiro; Matsuoka, Maya; Kimura, Satoko; Soma, Yoshinao; Nakano, Hajime

doi:10.1111/1346-8138.12648

Cited by 5 publications

(7 citation statements)

References 5 publications

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“…In the present case, the eruptions were not fully restricted to the pretibial region but were also observed on the calves and elbows. Such distribution of extended lesions to regions other than the pretibial have been reported in previous cases of DEB, pretibial …”

Section: Discussionsupporting

confidence: 83%

“…The previously reported COL7A1 mutations in DEB, pretibial, are summarized in Figure . Both recessive and dominant inheritance patterns have been observed in DEB, pretibial; one‐third of the reported cases showed a recessive inheritance pattern while two‐thirds showed a dominant inheritance pattern.…”

Section: Discussionmentioning

confidence: 95%

“…Such distribution of extended lesions to regions other than the pretibial have been reported in previous cases of DEB, pretibial. [2][3][4][5] Gene analysis revealed that the present patient was a compound heterozygote with a premature termination codon (PTC) mutation (p.R1933X) and a splice site mutation (c.6348+1G>A) that generated two aberrant in-frame transcripts in COL7A1. The p.R1933X mutation has already been reported to be a recurrent mutation of recessive DEB, including the Hallopeau-Siemens type, and a de novo p.R1933X mutation has also been reported.…”

Section: Discussionmentioning

confidence: 99%

“…The previously reported COL7A1 mutations in DEB, pretibial, are summarized in Figure 2. [2][3][4][5][7][8][9][10][11][12][13][14][15] Both recessive and dominant inheritance patterns have been observed in DEB, pretibial; onethird of the reported cases showed a recessive inheritance pattern while two-thirds showed a dominant inheritance pattern. While c.3840delC mutation, previously identified in both Hallopeau-Siemens type and non-Hallopeau-Siemens type DEB, was found in only two cases of DEB, pretibial, the COL7A1 mutations was highly diverse in DEB, pretibial, as with other DEB subtypes.…”

Section: Discussionmentioning

confidence: 99%

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Splice site mutation in COL7A1 resulting in aberrant in‐frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Masunaga

Kubo

Ishiko

2018

The Journal of Dermatology

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Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Splice site mutation in COL7A1 resulting in aberrant in‐frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Masunaga

Kubo

Ishiko

2018

The Journal of Dermatology

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“…[ =, Pro863_Gly904delinsArg])c20recessiveheterogeneous exon 20 skipRDEB-gen intermedslightly reducedthis paper and 5 4c.4011G>A (p.Gly1326_Pro1337del)3333recessivec.7769G>A (p.Gly2590Asp)104NArecessivehomogeneous exon 33 skipRDEB-gen intermedslightly reducedthis paper (EB-052)5c.4980+5G>C (p.Gly1646_Arg1660del)IVS5353recessivedeletion spanning COL7A1 + 15 other genes–NArecessivehomogeneous exon 53 skipRDEB-gen intermedunknown 45 6c.5820G>A (p.[ =, Gly1925_Pro1940del])7070recessivec.4039G>C (p.Gly1347Arg)34NArecessiveheterogeneous exon 70 skip, mutantRDEB-ac and RDEB-gen intermednormald46, 47recessivec.7474C>T (p.(Arg2492*))98NArecessiveheterogeneous exon 70 skipRDEB-gen intermedstrongly reduced 47 7c.5856G>C (p.Asn1941_Lys1952del)7171dominantc. =NANANAheterogeneous exon 71 skipDDEB-ptnormal 48 8c.6181-6T>G (p.Gly2061_Gln2072del)IVS7374dominantc. =NANANAheterogeneous exon 74 skipDDEB-gennormaldthis paper (EB-072)9c.6215del (p.Gly2061_Gln2072del)7474dominantc.…”

Section: Resultsmentioning

confidence: 99%

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

Bremer

Heijden

Eichhorn

et al. 2019

Molecular Therapy - Nucleic Acids

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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.

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A novel mutation of COL7A1 in a Chinese DEB‐Pt family and review of the literature

Jin

Xin

et al. 2019

J of Cosmetic Dermatology

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Background: Pretibial dystrophic epidermolysis bullosa (DEB-Pt) is an extremely rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by blistering and scar formation. The pathogenesis of the disease is mainly due to the mutation of COL7A1 gene encoding type VII collagen fibers, resulting in the destruction of the anchoring structure of the epidermis and dermis. Aims:The purpose of this study was to discover the major mutations in DEB-Pt by studying this family and reviewing the literature on DEB-Pt. Patients/Methods:We examined the patients by clinical manifestations and histopathology, extracted DNA from blood samples from 7 individuals in the family via FlexiGene DNA Kit, and then sequenced the samples using whole-exon sequencing (WES). Result:Characteristic clinical manifestations such as blisters and scars were found in the patients. Genetic analysis revealed a missense mutation in exon 87(c.6860G>A) of COL7A1 gene, which has never been reported before. Conclusion:The discovery of the new mutation extends the COL7A1 mutation database. We also reviewed all the mutation in DEB-Pt from relevant literature at home and abroad. This will facilitate the molecular diagnosis, treatment, and prognosis of DEB-Pt. K E Y W O R D Sbase mutation, COL7A1, dystrophic epidermolysis bullosa, pedigree, whole-exon sequencing

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Splicing mutation in the COL7A1 gene mRNA exon 71 in a female patient with pretibial epidermolysis bullosa

Cited by 5 publications

References 5 publications

Splice site mutation in COL7A1 resulting in aberrant in‐frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Splice site mutation in COL7A1 resulting in aberrant in‐frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

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

A novel mutation of COL7A1 in a Chinese DEB‐Pt family and review of the literature

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