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

Background Infection is an important complication of epidermolysis bullosa (EB), and Staphylococcus aureus has been pointed out as the most common pathogen among this population. The objective of this study was to investigate the prevalence and antimicrobial resistance profile of S. aureus colonizing EB patients in Brazil. Methods This cross‐sectional multicenter study was conducted between December 2015 and December 2017. We included a total of 89 individuals with EB from medical centers across Brazil. Data were obtained through clinical and bacteriological investigation. S. aureus were identified by biochemical tests. The nuc and mecA genes were confirmed by PCR assay. Antimicrobial susceptibility was investigated by disk diffusion method. Results The overall prevalence of S. aureus was 51.7% (46/89). Methicillin‐resistant S. aureus (MRSA) was detected in 24.7% (19/77) of all S. aureus isolates, colonizing 15.7% (14/89) of all patients. Community‐associated (CA)‐MRSA strains were resistant against sulfamethoxazole/trimethoprim and levofloxacin (P < 0.05%). S. aureus colonization of the nares and belly button represented a 3.4 times higher risk of simultaneous skin lesion colonization (P < 0.05%). Conclusions The high frequency of MRSA colonizing patients with EB is alarming considering its association with life‐threatening complications and poorer outcomes. EB patients are at increased risk of colonization and infection by Staphylococcus aureus and CA‐MRSA. Getting to know S. aureus carriage sites and its antimicrobial susceptibility profile is key when planning new individualized and more effective prophylactic and therapeutic measures.

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“…All patients were diagnosed as having EB through mutational analysis (NGS‐based multigene panel specific for EB) 18 …”

Section: Methodsmentioning

confidence: 99%

Prevalence and antimicrobial resistance profile of Staphylococcus aureus in inherited epidermolysis bullosa: a cross‐sectional multicenter study in Brazil

et al. 2021

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“…The present study was approved by the Ethics Committee of the Universidade Federal do Rio Grande do Sul (project 31 608) and F I G U R E 1 Congenital absence of skin in patients with epidermolysis bullosa Plataforma Brasil (protocol 2.481.885) and is part of a Brazilian project on EB coordinated by our research group. 9 3 | RESULTS AND DISCUSSION…”

Section: Methodsmentioning

confidence: 99%

Genotype‐phenotype correlations on epidermolysis bullosa with congenital absence of skin: A comprehensive review

et al. 2020

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Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype-phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype-phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch-like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non-collagenous interruptions of the triple-helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon.

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“… 7 It should be noted, however, that several other types of variants, in different combinations, have also been associated with this subtype. 67 , 79 , 81 , 82 , 83 , 84 The intermediate form is characterized the presence of at least one variant that allows for some type VII collagen production, thus enabling the assembly, even if partial, of the anchoring fibrils. Thus, the genetic changes associated with this subtype can affect the association of polypeptides, the formation and stability of the triple helix, or cause some conformational modification in the protein.…”

Section: Genetics Of Dystrophic Epidermolysis Bullosamentioning

confidence: 99%

“…86 , 87 , 88 Interestingly, the most described variants in cases of localized RDEB are those that occur in splice sites. 83 , 86 , 88 , 89 Splice variants are associated with a diversity of phenotypes, depending on their influence on the sequence of the protein formed. In the localized form, they usually result in the excision of whole exons (exon skipping), without altering the remaining protein sequence.…”

Section: Genetics Of Dystrophic Epidermolysis Bullosamentioning

confidence: 99%

Inherited epidermolysis bullosa: update on the clinical and genetic aspects

Mariath

Santin

Schüler‐Faccini

et al. 2020

Anais Brasileiros de Dermatologia

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Inherited epidermolysis bullosa is a group of genetic diseases characterized by skin fragility and blistering on the skin and mucous membranes in response to minimal trauma. Epidermolysis bullosa is clinically and genetically very heterogeneous, being classified into four main types according to the layer of skin in which blistering occurs: epidermolysis bullosa simplex (intraepidermal), junctional epidermolysis bullosa (within the lamina lucida of the basement membrane), dystrophic epidermolysis bullosa (below the basement membrane), and Kindler epidermolysis bullosa (mixed skin cleavage pattern). Furthermore, epidermolysis bullosa is stratified into several subtypes, which consider the clinical characteristics, the distribution of the blisters, and the severity of cutaneous and extracutaneous signs. Pathogenic variants in at least 16 genes that encode proteins essential for the integrity and adhesion of skin layers have already been associated with different subtypes of epidermolysis bullosa. The marked heterogeneity of the disease, which includes phenotypes with a broad spectrum of severity and many causal genes, hinders its classification and diagnosis. For this reason, dermatologists and geneticists regularly review and update the classification criteria. This review aimed to update the state of the art on inherited epidermolysis bullosa, with a special focus on the associated clinical and genetic aspects, presenting data from the most recent reclassification consensus, published in 2020.

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

Cited by 25 publications

References 75 publications

Prevalence and antimicrobial resistance profile of Staphylococcus aureus in inherited epidermolysis bullosa: a cross‐sectional multicenter study in Brazil

Prevalence and antimicrobial resistance profile of Staphylococcus aureus in inherited epidermolysis bullosa: a cross‐sectional multicenter study in Brazil

Genotype‐phenotype correlations on epidermolysis bullosa with congenital absence of skin: A comprehensive review

Inherited epidermolysis bullosa: update on the clinical and genetic aspects

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