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

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.

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Inherited Epidermolysis Bullosa: A case report

Journal of Universal College of Medical Sciences ◽

10.3126/jucms.v3i3.24248 ◽

2015 ◽

Vol 3 (3) ◽

pp. 39-42 ◽

Cited By ~ 1

Author(s):

Shyam Kumar Mahato ◽

Susana Lama ◽

Nikhil Agarwal ◽

Nagendra Chaudhary

Keyword(s):

Case Report ◽

Epidermolysis Bullosa ◽

Neonatal Period ◽

Heterogeneous Group ◽

Mechanical Trauma ◽

Epidermolysis Bullosa Simplex ◽

Blister Formation ◽

Inherited Epidermolysis Bullosa ◽

Genetically Determined ◽

Degrees Of Severity

Epidermolysis bullosa (EB) is a heterogeneous group of genetically determined, mechano-bullous disorders characterized by blister formation in response to mechanical trauma. The blistering of the skin occurs in the varying degrees of severity and can severely incapacitate the life of the afflicted patient. Epidermolysis Bullosa Simplex (EBS), the most commonly occurring type, is dominantly inherited where treatment still remains a major challenge. We report a newborn female with blistering of the skin during the immediate neonatal period.

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Advances in understanding the molecular basis of skin fragility

F1000Research ◽

10.12688/f1000research.12658.1 ◽

2018 ◽

Vol 7 ◽

pp. 279 ◽

Cited By ~ 1

Author(s):

Cristina Has

Keyword(s):

Epidermolysis Bullosa ◽

Molecular Basis ◽

Molecular Mechanisms ◽

Genetic Disorders ◽

Scientific Progress ◽

Mechanical Trauma ◽

Therapeutic Approaches ◽

New Genes ◽

Inherited Epidermolysis Bullosa ◽

Skin Fragility

Skin fragility refers to a large group of conditions in which the ability of the skin to provide protection against trivial mechanical trauma is diminished, resulting in the formation of blisters, erosions, wounds, or scars. Acquired and physiological skin fragility is common; genetic disorders are rare but give insight into the molecular mechanisms ensuring skin stability. The paradigm is represented by inherited epidermolysis bullosa. This review is focused on recent advances in understanding the molecular basis of genetic skin fragility, including emerging concepts, controversies, unanswered questions, and opinions of the author. In spite of the advanced knowledge on the genetic causes of skin fragility, the molecular pathology is still expanding. Open questions in understanding the molecular basis of genetic skin fragility are the following: what are the causes of phenotypes which remain genetically unsolved, and what are the molecular modifiers which might explain phenotypic differences among individuals with similar mutations? New mutational mechanisms and new genes have recently been discovered and are briefly described here. Comprehensive next-generation sequencing-based genetic testing improved mutation detection and facilitated the identification of the genetic basis of unclear and new phenotypes. Characterization of the biochemical and cell biological consequences of the genetic variants is challenging and laborious but may represent the basis for personalized therapeutic approaches. Molecular modifiers of skin fragility have been uncovered in particular animal and genetic models but not in larger cohorts of patients. This scientific progress is the basis for revisions of the epidermolysis bullosa classification and for innovative therapeutic approaches designed for this intractable condition.

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Hereditary Epidermolysis Bullosa: New Description

Dermatology and Dermatitis ◽

10.31579/2578-8949/066 ◽

2020 ◽

Vol 5 (1) ◽

pp. 01-02

Author(s):

Kaoutar Laamari ◽

Hanane Baybay ◽

Samia Mrabat ◽

Zakia Douhi ◽

Sara Elloudi ◽

...

Keyword(s):

Epidermolysis Bullosa ◽

Heterogeneous Group ◽

Mechanical Trauma ◽

Epidermolysis Bullosa Simplex ◽

Blister Formation ◽

Genetically Determined ◽

Hereditary Epidermolysis Bullosa ◽

Degrees Of Severity

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Case Report: Identification of a Novel Pathogenic Germline TP53 Variant in a Family With Li–Fraumeni Syndrome

Frontiers in Genetics ◽

10.3389/fgene.2021.734809 ◽

2021 ◽

Vol 12 ◽

Author(s):

Francesco Paduano ◽

Fernanda Fabiani ◽

Emma Colao ◽

Francesco Trapasso ◽

Nicola Perrotti ◽

...

Keyword(s):

Case Report ◽

Autosomal Dominant ◽

Liver Carcinoma ◽

The Novel ◽

Li Fraumeni Syndrome ◽

Pathogenic Variants ◽

Family Pedigree ◽

The Family ◽

Dominant Disease ◽

Li Fraumeni

Li–Fraumeni syndrome (LFS) is an inherited autosomal dominant disease characterized by a predisposition to many cancers. Germline pathogenic variants in TP53 are primarily responsible for LFS. By performing a targeted sequencing panel in a proband with liver carcinoma having a deceased son affected by osteosarcoma, we found the novel heterozygous frameshift variant c.645del (p.Ser215Argfs*32) in the TP53 gene. This variant co-segregated with typical LFS cancers in the family pedigree, consistent with the pathogenicity of this novel and previously undescribed TP53 variant.

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