Late-onset skin fragility in childhood: a case of junctional epidermolysis bullosa of late onset caused by a missense mutation inCOL17A1

2013 ◽  
Vol 169 (3) ◽  
pp. 714-715 ◽  
Author(s):  
S. Vanotti ◽  
C. Chiaverini ◽  
A. Charlesworth ◽  
N. Bonnet ◽  
P. Berbis ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Epidermolysis Bullosa ◽  
Late Onset ◽  
Junctional Epidermolysis Bullosa ◽  
Skin Fragility

scholarly journals A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 716
Author(s):  
Daniele Castiglia ◽  
Paola Fortugno ◽  
Angelo Giuseppe Condorelli ◽  
Sabina Barresi ◽  
Naomi De Luca ◽  
...  
Keyword(s):  
Amniotic Membrane ◽  
Epidermolysis Bullosa ◽  
Ocular Involvement ◽  
Human Amniotic Membrane ◽  
Vitro Assay ◽  
Junctional Epidermolysis Bullosa ◽  
Mucosal Involvement ◽  
Skin Fragility ◽  
Laminin 332

Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.

Junctional epidermolysis bullosa of late onset explained by mutations in COL17A1

2011 ◽  
Vol 164 (6) ◽  
pp. 1280-1284 ◽  
Author(s):  
W.Y. Yuen ◽  
H.H. Pas ◽  
R.J. Sinke ◽  
M.F. Jonkman
Keyword(s):  
Epidermolysis Bullosa ◽  
Late Onset ◽  
Junctional Epidermolysis Bullosa

Junctional epidermolysis bullosa without pyloric atresia due to a homozygous missense mutation in ITGB4

2018 ◽  
Vol 46 (2) ◽  
pp. e61-e63
Author(s):  
Kenji Yoshida ◽  
Mariko Sadamoto ◽  
Takashi Sasaki ◽  
Akiharu Kubo ◽  
Akira Ishiko
Keyword(s):  
Missense Mutation ◽  
Epidermolysis Bullosa ◽  
Pyloric Atresia ◽  
Junctional Epidermolysis Bullosa ◽  
Homozygous Missense Mutation

scholarly journals The Missense Mutation p.R1303Q in Type XVII Collagen Underlies Junctional Epidermolysis Bullosa Resembling Kindler Syndrome

2014 ◽  
Vol 134 (3) ◽  
pp. 845-849 ◽  
Author(s):  
Cristina Has ◽  
Dimitra Kiritsi ◽  
Jemima E. Mellerio ◽  
Claus-Werner Franzke ◽  
Emma Wedgeworth ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Epidermolysis Bullosa ◽  
Junctional Epidermolysis Bullosa ◽  
Kindler Syndrome ◽  
Xvii Collagen

A missense mutation (G1506E) in the adhesion G domain of laminin-5 causes mild junctional epidermolysis bullosa

2003 ◽  
Vol 309 (1) ◽  
pp. 96-103 ◽  
Author(s):  
Maria Scaturro ◽  
Patrizia Posteraro ◽  
Alessandro Mastrogiacomo ◽  
Maria Letizia Zaccaria ◽  
Naomi De Luca ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Epidermolysis Bullosa ◽  
Junctional Epidermolysis Bullosa ◽  
Laminin 5

scholarly journals Impaired Mitochondrial and Metabolic Function of Fibroblasts Derived from Patients with Recessive Dystrophic and Junctional Epidermolysis Bullosa

2020 ◽  
pp. 75-83
Author(s):  
Ilona Tietzová ◽  
Kirk Twaroski ◽  
Cindy Eide ◽  
Julie H. Ostrander ◽  
Peter Crawford ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Mitochondrial Function ◽  
Metabolic Stress ◽  
Mitochondrial Morphology ◽  
Energy Status ◽  
Inherited Disorders ◽  
Mitochondrial Energy Metabolism ◽  
Junctional Epidermolysis Bullosa ◽  
Skin Fragility ◽  
Skin Healing

Background: Recessive dystrophic epidermolysis bullosa (RDEB) and junctional EB (JEB) are inherited disorders characterised by fragility and blistering of epithelial tissues leading to pain, pruritus, and adherent scarring. The severity and chronic nature of the resultant skin wounds significantly reduces quality and length of life. Current therapies primarily consist of protective bandaging and nutritional supplementation; there is no cure for these disorders. Although the skin fragility results from a lack of C7 protein (RDEB) and laminin-332 (JEB), other serious aspects of these disorders, such as inflammation that interferes with healing and aggressive squamous cell carcinoma, have not been completely elucidated. Recent research has suggested that mitochondrial function plays a significant role in skin healing. Objective: To evaluate how mitochondrial function differs in patients with RDEB and JEB. Method: The energy status of RDEB and JEB patient-derived fibroblasts was determined by Seahorse analysis and metabolite production. The energetics and overall morphology of RDEB and JEB patient-derived fibroblasts were assayed as a measure of metabolic stress. Results: EB patient-derived fibroblasts showed impaired oxidative phosphorylation with concomitant compensation by glycolysis. Morphological parameters were altered in RDEB and JEB fibroblasts compared with controls. Conclusion: This is the first study to describe changes in mitochondrial energy metabolism, metabolic profile, and mitochondrial morphology of EB patients.

scholarly journals LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1055 ◽  
Author(s):  
Sarah Kiener ◽  
Aurore Laprais ◽  
Elizabeth A. Mauldin ◽  
Vidhya Jagannathan ◽  
Thierry Olivry ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Epidermolysis Bullosa ◽  
Clinical Signs ◽  
Autosomal Recessive Inheritance ◽  
Missense Variant ◽  
Loss Of Function ◽  
Junctional Epidermolysis Bullosa ◽  
Skin Fragility ◽  
Close Relatives ◽  
Tentative Diagnosis

In a highly inbred Australian Shepherd litter, three of the five puppies developed widespread ulcers of the skin, footpads, and oral mucosa within the first weeks of life. Histopathological examinations demonstrated clefting of the epidermis from the underlying dermis within or just below the basement membrane, which led to a tentative diagnosis of junctional epidermolysis bullosa (JEB) with autosomal recessive inheritance. Endoscopy in one affected dog also demonstrated separation between the epithelium and underlying tissue in the gastrointestinal tract. As a result of the severity of the clinical signs, all three dogs had to be euthanized. We sequenced the genome of one affected puppy and compared the data to 73 control genomes. A search for private variants in 37 known candidate genes for skin fragility phenotypes revealed a single protein-changing variant, LAMB3:c.1174T>C, or p.Cys392Arg. The variant was predicted to change a conserved cysteine in the laminin β3 subunit of the heterotrimeric laminin-322, which mediates the binding of the epidermal basement membrane to the underlying dermis. Loss-of-function variants in the human LAMB3 gene lead to recessive forms of JEB. We confirmed the expected co-segregation of the genotypes in the Australian Shepherd family. The mutant allele was homozygous in two genotyped cases and heterozygous in three non-affected close relatives. It was not found in 242 other controls from the Australian Shepherd breed, nor in more than 600 other controls. These data suggest that LAMB3:c.1174T>C represents the causative variant. To the best of our knowledge, this study represents the first report of a LAMB3-related JEB in domestic animals.

scholarly journals Multiple Skin Squamous Cell Carcinomas in Junctional Epidermolysis Bullosa Due to Altered Laminin-332 Function

2020 ◽  
Vol 21 (4) ◽  
pp. 1426
Author(s):  
Paola Fortugno ◽  
Angelo Giuseppe Condorelli ◽  
Elena Dellambra ◽  
Liliana Guerra ◽  
Francesca Cianfarani ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Epidermolysis Bullosa ◽  
Proteolytic Processing ◽  
Disulphide Bond ◽  
Structural Element ◽  
Junctional Epidermolysis Bullosa ◽  
Skin Fragility ◽  
Gene Expression Studies ◽  
Laminin 332

Variably reduced expression of the basement membrane component laminin-332 (α3aβ3γ2) causes junctional epidermolysis bullosa generalized intermediate (JEB-GI), a skin fragility disorder with an increased susceptibility to squamous cell carcinoma (SCC) development in adulthood. Laminin-332 is highly expressed in several types of epithelial tumors and is central to signaling pathways that promote SCC tumorigenesis. However, laminin-332 mutations and expression in individuals affected by JEB-GI and suffering from recurrent SCCs have been poorly characterized. We studied a JEB-GI patient who developed over a hundred primary cutaneous SCCs. Molecular analysis combined with gene expression studies in patient skin and primary keratinocytes revealed that the patient is a functional hemizygous for the p.Cys1171* mutant allele which is transcribed in a stable mRNA encoding for a β3 chain shortened of the last two C-terminal amino acids (Cys1171-Lys1172). The lack of the Cys1171 residue involved in the C-terminal disulphide bond to γ2 chain did not prevent assembly, secretion, and proteolytic processing of the heterotrimeric molecule. Immunohistochemistry of SCC specimens revealed accumulation of mutant laminin-332 at the epithelial-stromal interface of invasive front. We conclude that the C-terminal disulphide bond is a structural element crucial for laminin-332 adhesion function in-vivo. By saving laminin-332 amount, processing, and signaling role the p.Cys1171* mutation may allow intrinsic pro-tumorigenic properties of the protein to be conveyed, thus contributing to invasiveness and recurrence of SCCs in this patient.

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