Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

2021 ◽  
Vol 64 (12) ◽  
pp. 104345
Author(s):  
Mayank Nilay ◽  
Deepti Saxena ◽  
Kausik Mandal ◽  
Amita Moirangthem ◽  
Shubha R. Phadke
Keyword(s):  
Epidermolysis Bullosa ◽  
Pathogenic Variants

Coinheritance of 2 New Potentially Damaging Heterozygous COL7A1 Variants in a Family With Autosomal Dominant Epidermolysis Bullosa Pruriginosa

2018 ◽  
Vol 21 (6) ◽  
pp. 580-584
Author(s):  
Gordon I Hale ◽  
Marta C Cohen ◽  
Oliver W Quarrell ◽  
John A McGrath ◽  
Andrew G Messenger
Keyword(s):  
Epidermolysis Bullosa ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Phenotypic Variability ◽  
Incomplete Penetrance ◽  
Histopathological Diagnosis ◽  
Delayed Presentation ◽  
Pathogenic Variants ◽  
Type Vii Collagen ◽  
Phenotypic And Genotypic Variability

Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of EB which is characterized by intense pruritus with blistering and nodular or lichenoid lesions most prominent on the lower extremities. It is caused by variants in COL7A1 which encodes for type VII collagen. There is wide phenotypic and genotypic variability between affected individuals. We report 2 potentially pathogenic variants in COL7A1 occurring on the same allele in a family with EBP and autosomal dominant inheritance. Late-onset EBP and incomplete penetrance may lead to delayed presentation in affected family members with the same variants. The broad phenotypic variability seen in EBP suggests that further genotypic and environmental factors may influence presentation. Genetic and histopathological diagnosis is essential, given the considerable overlap with clinically similar presentations such as hypertrophic lichen planus.

scholarly journals A Familial Form of Epidermolysis Bullosa Simplex Associated with a Pathogenic Variant in KRT5

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1503
Author(s):  
Francesco Paduano ◽  
Emma Colao ◽  
Teresa Grillone ◽  
Marco Flavio Michele Vismara ◽  
Rosario Amato ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Mechanical Stability ◽  
Pathogenic Variant ◽  
Mechanical Trauma ◽  
Epidermolysis Bullosa Simplex ◽  
Pathogenic Variants ◽  
Family Pedigree ◽  
Familial Form ◽  
The Family ◽  
Skin Fragility

Epidermolysis bullosa simplex is a disease that belongs to a group of genodermatoses characterised by the formation of superficial bullous lesions caused by minor mechanical trauma to the skin. The skin fragility observed in the EBS is mainly caused by pathogenic variants in the KRT5 and KRT14 genes that compromise the mechanical stability of epithelial cells. By performing DNA sequencing in a female patient with EBS, we found the pathogenic variant c.967G>A (p.Val323Met) in the KRT5 gene. This variant co-segregated with EBS in the family pedigree and was transmitted in an autosomal dominant inheritance manner. This is the first report showing a familial form of EBS due to this pathogenic variant.

scholarly journals Identification and Computational Analysis of Novel Pathogenic Variants in Pakistani Families with Diverse Epidermolysis Bullosa Phenotypes

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 620
Author(s):  
Fehmida F. Khan ◽  
Naima Khan ◽  
Sakina Rehman ◽  
Amir Ejaz ◽  
Uzma Ali ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Low Frequencies ◽  
Pakistani Population ◽  
3 Dimensional ◽  
Pathogenic Variants ◽  
First Case ◽  
Whole Exome ◽  
Different Types ◽  
Pakistani Families ◽  
In Silico Analyses

Epidermolysis bullosa (EB) includes a group of rare gesnodermatoses that result in blistering and erosions of the skin and mucous membranes. Genetically, pathogenic variants in around 20 genes are known to alter the structural and functional integrity of intraepidermal adhesion and dermo-epidermal anchorage, leading to four different types of EB. Here we report the underlying genetic causes of EB phenotypes segregating in seven large consanguineous families, recruited from different regions of Pakistan. Whole exome sequencing, followed by segregation analysis of candidate variants through Sanger sequencing, identified eight pathogenic variants, including three novel (ITGB4: c.1285G>T, and c.3373G>A; PLEC: c.1828A>G) and five previously reported variants (COL7A1: c.6209G>A, and c.1573C>T; FERMT1: c.676insC; LAMA3: c.151insG; LAMB3: c.1705C>T). All identified variants were either absent or had very low frequencies in the control databases. Our in-silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Intriguingly, we report the first case of a recessively inherited form of rare EBS-Ogna associated with a homozygous variant in the PLEC gene. Our study highlights the clinical and genetic diversity of EB in the Pakistani population and expands the mutation spectrum of EB; it could also be useful for prenatal diagnosis and genetic counseling of the affected families.

Structure, compositon and function of the dermal-epidermal junction: Relevance in cutaneous disease and diagnosis

1989 ◽  
Vol 47 ◽  
pp. 868-869
Author(s):  
K. A. Holbrook
Keyword(s):  
Basement Membrane ◽  
Epidermolysis Bullosa ◽  
Normal Skin ◽  
Lamina Densa ◽  
Inherited Disorders ◽  
Ultrastructural Studies ◽  
Type Iv ◽  
Type Vii Collagen ◽  
Attachment Structures ◽  
Matrix Components

The dermal-epidermal junction (DEJ), or basement membrane rone, is the boundary between the epithelial and mesenchymal compartments of the skin; epidermal and fibroblastic cells in these two regions collaborate to synthesire its components. Ultrastructural studies (TEM and SEM) have defined a series of planes or layers (basal epidermal, lamina lucida, lamina densa, sublamina densa) and the morphology and density of attachment structures (hemidesmosomes, anchoring filaments, anchoring fibrils and anchoring plaques) in this region of normal skin. Change in structure of the DEJ provides information about the history of the tissue; reduplication of the lamina densa, for example, indicates a site of cell detachment or migration, or remodelling that accompanies repair of focal damage. In normal skin the structure of the DEJ is stable; in pathologic conditions it can be compromised by the congenital absence of certain structures or antigens (e.g., in the inherited disorders, epidermolysis bullosa [EB]) or by enzymatic degradation (e.g., in tumor invasion). Dissolution of the DEJ can also occur normally during the formation of epidermal appendages (e.g., hair follicles) and as melanocytes and Langerhans cells migrate into the epidermis during development.Biochemical and immunohisto/cytochemical studies have identified more than 20 molecules at the DEJ. These include well known matrix molecules (e.g., types IV and V collagen, laminin and fibronectin) and skin-specific antigens. The latter have been identified by autoantibodies or specific polyclonal or monoclonal antibodies raised against the skin, cultured cells and other epithelia. Some of the molecules of the DEJ are are present in basement membrane zones of many epithelia and thus are considered ubiquitous components (type IV, V, laminin, fibronectin, nidogen, entactin, HSPG, LDA-1, CSP [3B3]). All of them (that have been investigated in developing skin) appear ontogenetically as early as human embryonic tissue can be obtained and their expression is typically normal in patients with EB. The known properties of many of these molecules (particularly the matrix components) suggest functions they might impart to the DEJ: support of an epithelium (type IV collagen), regulation of permeability (heparan sulfate proteoglycan) or facilitation of cell attachment (fibronectin) and movement (laminin). Another group of matrix components and antigens of the DEJ includes molecules that are skin-specific or characteristic of stratified squamous epithelia (type VII collagen=LH 7:2 antigen, bullous pemphigoid antigen, AA3, GB3, KF-1,19-DEJ-1, epidermolysis bullosa acquisita antigen [EBA], AF-1 and AF-2, cicatricial pemphigoid antigen [CPA]) . These molecules are expressed in the DEJ later in development than the first group of molecules, in conjunction with the morphologic appearance of the structure they represent. Their appearance is also coordinated with specific developmental events (e.g., epidermal stratification) and the expression of molecules of differentiation in the epidermis and dermis. One or more of them is typically absent or reduced in expression in the skin of patients with heritable disorders affecting this region. There is no apparent correlation between the location of molecules in the DEJ and the stability of their expression.

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