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Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families

Background: Dystrophic Epidermolysis bullosa (DEB) is a rare, severe subtype of epidermolysis bullosa (EB), characterized by blisters and miliary rashes of the skin. Dystrophic EB (DEB) includes variants inherited both in an autosomal-dominant or autosomal-recessive manner. Recessive dystrophic EB (...

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Autores principales: Fozia, Fozia, Nazli, Rubina, Alrashed, May Mohammed, Ghneim, Hazem K., Haq, Zia Ul, Jabeen, Musarrat, Alam Khan, Sher, Ahmad, Ijaz, Bourhia, Mohammed, Aboul-Soud, Mourad A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316163/
https://www.ncbi.nlm.nih.gov/pubmed/35885431
http://dx.doi.org/10.3390/diagnostics12071525
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author Fozia, Fozia
Nazli, Rubina
Alrashed, May Mohammed
Ghneim, Hazem K.
Haq, Zia Ul
Jabeen, Musarrat
Alam Khan, Sher
Ahmad, Ijaz
Bourhia, Mohammed
Aboul-Soud, Mourad A. M.
author_facet Fozia, Fozia
Nazli, Rubina
Alrashed, May Mohammed
Ghneim, Hazem K.
Haq, Zia Ul
Jabeen, Musarrat
Alam Khan, Sher
Ahmad, Ijaz
Bourhia, Mohammed
Aboul-Soud, Mourad A. M.
author_sort Fozia, Fozia
collection PubMed
description Background: Dystrophic Epidermolysis bullosa (DEB) is a rare, severe subtype of epidermolysis bullosa (EB), characterized by blisters and miliary rashes of the skin. Dystrophic EB (DEB) includes variants inherited both in an autosomal-dominant or autosomal-recessive manner. Recessive dystrophic EB (RDEB) is divided into many subtypes and prevails as a result of biallelic genetic mutations in COL7A1 gene encoding type VII collagen, a major stabilizing molecule of the dermo-epidermal junction. The blister formation is mainly due to the variable structural and functional impairment of anchoring fibrils in VII collagen (COLVII), responsible for the adhesion of the epidermis to the dermis. Method: Three Pakistani families (A, B and C) affected with congenital dystrophic epidermolysis bullosa were recruited in the present study. The whole-exome sequencing (WES) approach was utilized for the detection of the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: This study identified a novel missense variant c.7034G>A, p. Gly2345Asp in exon 91, a novel Frameshift mutation c.385del (p. His129MetfsTer18) in a homozygous form in exon no 3, and a previously known nonsense variation (c.1573 C>T; p. Arg525Ter) in exon 12 of COL7A1 gene in families A, B, and C, respectively, as causative mutations responsible for dystrophic epidermolysis bullosa in these families. Conclusion: Our study validates the involvement of the COL7A1 gene in the etiology of dystrophic epidermolysis bullosa. It further expands the COL7A1 gene mutation database and provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes for EB patients.
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spelling pubmed-93161632022-07-27 Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families Fozia, Fozia Nazli, Rubina Alrashed, May Mohammed Ghneim, Hazem K. Haq, Zia Ul Jabeen, Musarrat Alam Khan, Sher Ahmad, Ijaz Bourhia, Mohammed Aboul-Soud, Mourad A. M. Diagnostics (Basel) Article Background: Dystrophic Epidermolysis bullosa (DEB) is a rare, severe subtype of epidermolysis bullosa (EB), characterized by blisters and miliary rashes of the skin. Dystrophic EB (DEB) includes variants inherited both in an autosomal-dominant or autosomal-recessive manner. Recessive dystrophic EB (RDEB) is divided into many subtypes and prevails as a result of biallelic genetic mutations in COL7A1 gene encoding type VII collagen, a major stabilizing molecule of the dermo-epidermal junction. The blister formation is mainly due to the variable structural and functional impairment of anchoring fibrils in VII collagen (COLVII), responsible for the adhesion of the epidermis to the dermis. Method: Three Pakistani families (A, B and C) affected with congenital dystrophic epidermolysis bullosa were recruited in the present study. The whole-exome sequencing (WES) approach was utilized for the detection of the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: This study identified a novel missense variant c.7034G>A, p. Gly2345Asp in exon 91, a novel Frameshift mutation c.385del (p. His129MetfsTer18) in a homozygous form in exon no 3, and a previously known nonsense variation (c.1573 C>T; p. Arg525Ter) in exon 12 of COL7A1 gene in families A, B, and C, respectively, as causative mutations responsible for dystrophic epidermolysis bullosa in these families. Conclusion: Our study validates the involvement of the COL7A1 gene in the etiology of dystrophic epidermolysis bullosa. It further expands the COL7A1 gene mutation database and provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes for EB patients. MDPI 2022-06-23 /pmc/articles/PMC9316163/ /pubmed/35885431 http://dx.doi.org/10.3390/diagnostics12071525 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fozia, Fozia
Nazli, Rubina
Alrashed, May Mohammed
Ghneim, Hazem K.
Haq, Zia Ul
Jabeen, Musarrat
Alam Khan, Sher
Ahmad, Ijaz
Bourhia, Mohammed
Aboul-Soud, Mourad A. M.
Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families
title Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families
title_full Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families
title_fullStr Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families
title_full_unstemmed Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families
title_short Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families
title_sort detection of novel biallelic causative variants in col7a1 gene by whole-exome sequencing, resulting in congenital recessive dystrophic epidermolysis bullosa in three unrelated families
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316163/
https://www.ncbi.nlm.nih.gov/pubmed/35885431
http://dx.doi.org/10.3390/diagnostics12071525
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