Analysis of the COL7A1 gene in Czech patients with dystrophic epidermolysis bullosa reveals novel and recurrent mutations

Jeřábková, Barbora; Kopečková, Lenka; Bučková, Hana; Veselý, Karel; Valíčková, Jana; Fajkusová, Lenka

doi:10.1016/j.jdermsci.2010.05.007

Cited by 11 publications

(6 citation statements)

References 8 publications

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“…The c.6205C > T variant has been described in a few cases of the RDEB inversa subtype in the Iranian and Japanese populations [12][13][14]. These mutations were quite frequently detected in the European population, both separately and in the combination with c. 425A > G [15][16][17]. Patient d3 represents the rare case of the combination of the RDEB pathological mutation in exon 111 c.8245G > A (p.G2749R, rs121912853) in a homozygous state (Clin-VAR accession VCV000017460) with the second heterozygous mutation in the KRT5 of c.1054C > T p.R352C (Supplementary Figure S4D,E).…”

Section: Mutations In the Col7a1 Genementioning

confidence: 98%

Signatures of Dermal Fibroblasts from RDEB Pediatric Patients

Beilin

Евтушенко

Lukyanov

et al. 2021

IJMS

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The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.

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Section: Mutations In the Col7a1 Genementioning

confidence: 98%

Signatures of Dermal Fibroblasts from RDEB Pediatric Patients

Beilin

Евтушенко

Lukyanov

et al. 2021

IJMS

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“…The relative type VII collagen deposition at the basement membrane zone, and the number and ultra-structure of anchoring fibrils can be assessed by immunofluorescence (IF) and electron microscopy (EM) techniques, respectively. Genotype-phenotype correlation has been extensively studied for the major subtypes of DEB [Abu Sa'd et al, 2006;Almaani et al, 2011;Dang et al, 2007;Escámez et al, 2010;Fine et al, 2008;Gardella et al, 2002;Hovnanian et al, 1997;Jeřábková et al, 2010;Kern et al, 2006Kern et al, , 2009Ouragini et al, 2010;Salas-Alanis et al, 2000;Sawamura et al, 2005;Van den Akker et al, 2009;Varki et al, 2007]. These studies have revealed that severe generalized RDEB is generally caused by bi-allelic mutations that result in a premature termination codon (PTC) (i.e., nonsense mutations, frame-shifting deletions, insertions/duplications, indels, and certain splice-site mutations).…”

Section: Dystrophic Epidermolysis Bullosa and The Type VII Collagen Gmentioning

confidence: 99%

“…Although a few recurrent mutations have been identified in several populations due to founder effects [Csikós et al, 2005;Escámez et al, 2010;Gardella et al, 2002;Jeřábková et al, 2010;Kern et al, 2006;Mellerio et al, 1997;Mohammedi et al, 1999;Murata et al, 2004;Salas-Alanis et al, 2000;Tamai et al, 1999], most families carry unique mutations, explaining the large number of different mutations identified so far. Most dominant mutations can cause heterogeneous phenotypes [Mellerio et al, 1998], while the clinical consequences for recessive mutations depend on the exact constellation of the genotype, in which the least "severe" mutation usually determines the phenotype Dunnill et al, 1996;Winberg et al, 1997].…”

Section: Dystrophic Epidermolysis Bullosa and The Type VII Collagen Gmentioning

confidence: 99%

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

et al. 2011

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Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder that can be inherited autosomal dominantly (DDEB) or recessively (RDEB) and covers a group of several distinctive phenotypes. A large number of unique COL7A1 mutations have been shown to underlie DEB. Although general genotype-phenotype correlation rules have emerged, many exceptions to these rules exist, compromising disease diagnosing and genetic counseling. We therefore constructed the International DEB Patient Registry (http://www.deb-central.org), aimed at worldwide collection and sharing of phenotypic and genotypic information on DEB. As of May 2011, this MOLGENIS-based registry contains detailed information on 508 published and 71 unpublished patients and their 388 unique COL7A1 mutations, and includes all combinations of mutations. The current registry RDEB versus DDEB ratio of 4:1, if compared to prevalence figures, suggests underreporting of DDEB in the literature. Thirty-eight percent of mutations stored introduce a premature termination codon (PTC) and 43% an amino acid change. Submission wizards allow users to quickly and easily share novel information. This registry will be of great help in disease diagnosing and genetic counseling and will lead to novel insights, especially in the rare phenotypes of which there is often lack of understanding. Altogether, this registry will greatly benefit the DEB patients.

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“…DDEB is usually associated to glycine substitutions within the triple helix of COL7A1 , although other missense mutations, deletions and splice‐site mutations have been reported in several rare cases . In RDEB, mutations include nonsense, splice site, deletions or insertions, and missense variants . Although glycine substitutions are primarily associated to DDEB, some of them act recessively, and, to add more complexity, some specific glycine substitutions were reported in both DDEB and RDEB…”

Section: Introductionmentioning

confidence: 99%

“…12 In RDEB, mutations include nonsense, splice site, deletions or insertions, and missense variants. 12,13 Although glycine substitutions are primarily associated to DDEB, some of them act recessively, and, to add more complexity, some specific glycine substitutions were reported in both DDEB and RDEB. 14 In KS, there is a mixed pattern of blistering, as cleavage can occur within the basal keratinocytes, within the lamina lucida or below the lamina densa.…”

Section: Introductionmentioning

confidence: 99%

An overview of the genetic basis of epidermolysis bullosa in Brazil: discovery of novel and recurrent disease‐causing variants

et al. 2019

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Epidermolysis bullosa (EB) is a genodermatosis that encompasses a group of clinically and genetically heterogeneous disorders classified in four major types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome. Our aim was to characterize recurrent and novel mutations associated to EB in a sample of Brazilian patients. Eighty‐seven patients (25 EBS, 4 JEB and 58 DEB) were studied. We performed a next‐generation sequencing‐based multigene panel through ion torrent technology including 11 genes: KRT5, KRT14, PLEC, TGM5, LAMA3, LAMB3, LAMC2, COL17A1, ITGB4, COL7A1, and FERMT1. A total of 72 different pathogenic or likely pathogenic variants were identified, 32 of them are novel. The causal variant was detected in 82 patients (efficiency of 94.3%). Pathogenic variants in the residue 125 of KRT14 were identified in 32% of all EBS patients. In DEB patients, four COL7A1 variants were quite frequent, some of them clustered in specific Brazilian regions. Our study extends the spectrum of known mutations in EB and describes, for the first time, the genetic profile of EB patients from Brazil.

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Analysis of the COL7A1 gene in Czech patients with dystrophic epidermolysis bullosa reveals novel and recurrent mutations

Cited by 11 publications

References 8 publications

Signatures of Dermal Fibroblasts from RDEB Pediatric Patients

Signatures of Dermal Fibroblasts from RDEB Pediatric Patients

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

An overview of the genetic basis of epidermolysis bullosa in Brazil: discovery of novel and recurrent disease‐causing variants

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