title: Erythrokeratoderma variabilis without connexin 31 or connexin 30.3 gene mutation: immunohistological, ultrastructural and genetic studies.
abstract: Erythrokeratoderma variabilis, characterized by migrating erythema and fixed keratotic plaques, is a rare congenital disorder which has recently been connected with connexin (Cx)30.3 or Cx31 gene mutations. We present a 9-month-old Japanese girl who exhibited the typical clinical features of the disease, but carried no Cx30.3 or Cx31 gene mutations. Histopathologically, regular acanthosis with hyperkeratosis and hypergranulosis was observed in her lesional skin. Upregulation of involucrin and loricrin expression, and a weak expression of Cx26 was immunohistochemically observed in the upper spinous and granular layers. Electron microscopy revealed no abnormality in the keratin filaments, cornified cell envelope or gap junctions. Direct sequencing revealed no pathogenetic mutations in the Cx26, Cx30.3, Cx31 or Cx31.1 genes in this patient. The results indicate that erythrokeratoderma variabilis is pathologically heterogeneous, and that abnormalities in keratinization other than Cx30.3 and 31 gene mutations may underlie some forms of this disease.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. ariken@med.hokudai.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Arita
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Takashi
authors.initials: T
authors.lastname: Onozuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004890:Erythema / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D012867:Skin / Q000473:pathology / Q000648:ultrastructure
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; C068044:GJB3 protein, human; C076275:connexin 30.3