Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing
Dystrophic epidermolysis bullosa is an inherited skin disorder characterized by fragile skin that is prone to blistering. We report here a consanguineous Pakistani family with two siblings, in whom a severe recessive dystrophic epidermolysis bullosa was suspected. Using whole-exome sequencing for on...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Medical Journals Sweden
2020-09-01
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| Series: | Acta Dermato-Venereologica |
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| Online Access: |
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3634
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| _version_ | 1798017740963840000 |
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| author | Syed Ashraf Uddin Nicole Cesarato Aytaj Humbatova Axel Schmidt Fazal urRehman Muhammad Naeem Abdul Samad Tareen Sabrina Wolf Muhammad Anwar Panezai Holger Thiele Abdul Wali Regina Fölster-Holst Sulman Basit Muhammad Ayub Regina C. Betz |
| author_facet | Syed Ashraf Uddin Nicole Cesarato Aytaj Humbatova Axel Schmidt Fazal urRehman Muhammad Naeem Abdul Samad Tareen Sabrina Wolf Muhammad Anwar Panezai Holger Thiele Abdul Wali Regina Fölster-Holst Sulman Basit Muhammad Ayub Regina C. Betz |
| author_sort | Syed Ashraf Uddin |
| collection | DOAJ |
| description | Dystrophic epidermolysis bullosa is an inherited skin disorder characterized by fragile skin that is prone to blistering. We report here a consanguineous Pakistani family with two siblings, in whom a severe recessive dystrophic epidermolysis bullosa was suspected. Using whole-exome sequencing for one sibling, the homozygous base substitution c.7249C>G in COL7A1 was identified, and could be confirmed in the other sibling by Sanger sequencing. In our exome data, this mutation was annotated as a missense substitution (p.Gln2417Glu), but in silico tools indicated a possible effect on splicing. Using the ExonTrap vector it was verified that the mutation leads to activation of a cryptic donor splice site, which leads to loss of 26 nucleotides, and a frameshift event predicted to result in a truncated protein (p.Q2417Sfs*57). The present report describes an apparent COL7A1 missense substitution with an unexpected consequence on splicing that leads to a severe recessive dystrophic epidermolysis bullosa phenotype. |
| first_indexed | 2024-04-11T16:12:12Z |
| format | Article |
| id | doaj.art-bd4f63c7928444829e12ffa91cf0efd2 |
| institution | Directory Open Access Journal |
| issn | 0001-5555 1651-2057 |
| language | English |
| last_indexed | 2024-04-11T16:12:12Z |
| publishDate | 2020-09-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Dermato-Venereologica |
| spelling | doaj.art-bd4f63c7928444829e12ffa91cf0efd22022-12-22T04:14:39ZengMedical Journals SwedenActa Dermato-Venereologica0001-55551651-20572020-09-0110016adv0027510.2340/00015555-36345882Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on SplicingSyed Ashraf Uddin0Nicole CesaratoAytaj HumbatovaAxel SchmidtFazal urRehmanMuhammad NaeemAbdul Samad TareenSabrina WolfMuhammad Anwar PanezaiHolger ThieleAbdul WaliRegina Fölster-HolstSulman BasitMuhammad AyubRegina C. Betz Dystrophic epidermolysis bullosa is an inherited skin disorder characterized by fragile skin that is prone to blistering. We report here a consanguineous Pakistani family with two siblings, in whom a severe recessive dystrophic epidermolysis bullosa was suspected. Using whole-exome sequencing for one sibling, the homozygous base substitution c.7249C>G in COL7A1 was identified, and could be confirmed in the other sibling by Sanger sequencing. In our exome data, this mutation was annotated as a missense substitution (p.Gln2417Glu), but in silico tools indicated a possible effect on splicing. Using the ExonTrap vector it was verified that the mutation leads to activation of a cryptic donor splice site, which leads to loss of 26 nucleotides, and a frameshift event predicted to result in a truncated protein (p.Q2417Sfs*57). The present report describes an apparent COL7A1 missense substitution with an unexpected consequence on splicing that leads to a severe recessive dystrophic epidermolysis bullosa phenotype. https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3634 epidermolysis bullosa exome sequencing missense mutation splicing col7a1 |
| spellingShingle | Syed Ashraf Uddin Nicole Cesarato Aytaj Humbatova Axel Schmidt Fazal urRehman Muhammad Naeem Abdul Samad Tareen Sabrina Wolf Muhammad Anwar Panezai Holger Thiele Abdul Wali Regina Fölster-Holst Sulman Basit Muhammad Ayub Regina C. Betz Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing Acta Dermato-Venereologica epidermolysis bullosa exome sequencing missense mutation splicing col7a1 |
| title | Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing |
| title_full | Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing |
| title_fullStr | Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing |
| title_full_unstemmed | Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing |
| title_short | Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing |
| title_sort | apparent missense variant in col7a1 causes a severe form of recessive dystrophic epidermolysis bullosa via effects on splicing |
| topic | epidermolysis bullosa exome sequencing missense mutation splicing col7a1 |
| url |
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3634
|
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