This report describes general characteristics of erythrokeratodermia variabilis et progressiva 1 (EKVP1); most cases of EKVP1 exhibit autosomal dominant inheritance; one family has been reported with autosomal recessive inheritance. The human gene implicated in this disease is GJB3, which encodes connexin 31, a protein involved in the formation of gap junctions. Mutations in GJB3 are also associated with several forms of deafness (MIM:612644, MIM:220290). No gene orthologous to GJB3 has been identified in Drosophila.
UAS constructs of the human Hsap\GJB3 gene have been introduced into flies, including wild-type and a gene carrying a mutational lesion implicated in EKVP1. Variant(s) implicated in human disease tested (as transgenic human gene, GJB3): the F137L variant form has been introduced into flies. Introduction of the mutated copy leads to embryonic lethality or to lack of pigmentation in ommatidia and ommatidial degeneration when expressed only in the eye. Co-expression of candidate fly genes rescues the degeneration phenotype.
[updated Jul. 2017 by FlyBase; FBrf0222196]
[ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA 1; EKVP1](https://omim.org/entry/133200)
[GAP JUNCTION PROTEIN, BETA-3; GJB3](https://omim.org/entry/603324)
The erythrokeratodermias are a clinically variable and genetically heterogeneous group of inherited disorders characterized by widespread erythematous plaques, stationary or migratory, associated with nonmigratory hyperkeratoses (summary by Ishida-Yamamoto et al., 1997, pubmed:9326323). The condition is usually present at birth or occurs during the first year but may begin later in childhood or even in early adulthood. Lesions preferentially affect the face, buttocks, and extensor surfaces of the limbs. Palmoplantar keratoderma occurs in about half the cases, but hair, nails, and teeth are not affected (summary by Macfarlane et al., 1991, pubmed:1828175).
Erythrokeratodermia variabilis et progressiva (EKVP) is a skin disorder that is present at birth or becomes apparent in infancy. Although its signs and symptoms vary, the condition is characterized by two major features. The first is areas of hyperkeratosis, which is rough, thickened skin. These thickened patches are usually reddish-brown and can be widespread over many parts of the body or occur only in a small area. The patches tend to be fixed but can vary in size and shape, and in some affected people get larger over time. The areas of thickened skin are generally symmetric.
The second major feature of EKVP is patches of reddened skin called erythematous areas. Unlike the hyperkeratosis that occurs in this disorder, the erythematous areas are usually transient. They vary in size, shape, and location, and can occur anywhere on the body. The redness can be triggered by sudden changes in temperature, emotional stress, or trauma or irritation to the area. It usually fades within hours to days. [from Genetics Home Reference, GHR:condition:erythrokeratodermia variabilis et progressiva, 2016.4.28]
Erythrokeratodermia variabilis et progressiva is inherited as an autosomal dominant. There are also rare recessive forms of the disease. [from Genetics Home Reference, GHR:condition:erythrokeratodermia variabilis et progressiva, 2016.4.28]
Connexin is expressed in the skin, peripheral nerves and the cochlea. EKVP-associated Cx31 mutations have been proposed to cause trafficking defects with retention in the cytoplasm and cell death, endoplasmic reticulum stress-mediated cell death, and constitutive active-hemichannels and necrotic cell death (Ishida-Yamamoto, PMID:26945536).
No Drosophila orthologs.
