No function (updated: Oct. 10, 2018)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
This protein is annotated as membranous in Gene Ontology.
Total structural coverage: 28%
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The reference OMIM entry for this protein is 131760
Epidermolysis bullosa simplex, dowling-meara type; ebsdm
Epidermolysis bullosa herpetiformis, dowling-meara type
Epidermolysis bullosa simplex, generalized severe
A number sign (#) is used with this entry because the Dowling-Meara type of epidermolysis bullosa simplex (EBSDM) can be caused by mutation in either the keratin-5 (KRT5; 148040) or the keratin-14 (KRT14; 148066) gene.
DESCRIPTION
Epidermolysis bullosa simplex (EBS) is a clinically and genetically heterogeneous skin disorder characterized by recurrent blistering of the skin following minor physical trauma as a result of cytolysis within basal epidermal cells. Most forms show autosomal dominant inheritance. The Dowling-Meara type of EBS is the most severe form, with generalized blistering that often occurs in clusters (herpetiform), is often associated with hyperkeratosis of the palms and soles, and shows clumping of keratin filaments in basal epidermal cells. The other 2 main types of EBS include the milder generalized Koebner type (
131900) and the milder and localized Weber-Cockayne type (
131800) (Fine et al., 2008). All 3 forms can be caused by mutation in the KRT5 or the KRT14 gene. See
601001 for a rare autosomal recessive form caused by mutation in the KRT14 gene.
CLINICAL FEATURES
Dowling and Meara (1954) first described a form of epidermolysis bullosa simplex that resembled dermatitis herpetiformis (
601230). Onset of generalized bullae in a herpetiform (arciform) arrangement occurred during the first 3 months of life. Serous and hemorrhagic blisters could occur on any part of the body, but most frequently on the palms and soles, around the mouth, and on the trunk and neck. In general, the lesions healed without scarring, but pronounced inflammatory reactions, especially seen in hemorrhagic blisters, was accompanied by milia and occasional scar formation. Anton-Lamprecht and Schnyder (1982) reported a 2-year-old girl of Turkish origin with congenital generalized blister formation in a herpetiform arrangement. Direct immunofluorescence ruled out juvenile dermatitis herpetiformis. Ultrastructural investigation of a fresh blister and clinically intact preblistering skin revealed intraepidermal blister formation via cytolysis of basal cells, preceded by clumping of tonofilaments and partial attachment to the hemidesmosomes at the dermo-epidermal junction. This type of blister formation was significantly different from all other epidermolysis bullosa types and was a characteristic feature of the Dowling-Meara type of EBS. McGrath et al. (1992) reviewed the clinicopathologic features of 22 cases varying in age from 5 days to 46 years. All cases presented clinically within the first 5 days of life. Early blisters were often large (up to 5 cm in diameter), and were mostly acral and particularly periungual. Some patients presented with more widespread erosive skin changes, and 2 neonates with extensive skin involvement died as a result of overwhelming sepsis. After the neonatal period, the pattern of blistering became more proximal, with hemorrhagic, herpetiform clusters of blisters. Central healing with recurrent blistering at the margins of these areas was frequent. Other physical signs included varying degrees of intraoral blistering, nail shedding, nail dystrophy, minor scarring, palmoplantar keratoderma, a lack of seasonal variation, and improvement during later childhood. Basal cell cytolysis in association with clumping of tonofilaments was the underlying pathologic mechanism. The clumping was found even in some nonlesional skin, suggesting that it is of primary pathogenetic significance. The disease was occasi ...
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Subscribe to this protein entry history
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 131760 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).