Epidermolysis Bullosa Simplex, Ogna Type

A number sign (#) is used with this entry because of evidence that the Ogna type of epidermolysis bullosa simplex (EBSOG) is caused by heterozygous mutation in the PLEC1 gene (601282) on chromosome 8q24.

Clinical Features

This form of EBS was identified by Gedde-Dahl (1971) in a large Norwegian kindred living in the town of Ogna. It was differentiated from the more generalized form of Koebner (131900) and the localized form of Weber and Cockayne (131800) by the occurrence of skin bruising in the Ogna type.

Gedde-Dahl (1977) identified 97 cases in the Norwegian kindred. He suggested that the first family of Cockayne (see 131800) may have had the Ogna form.

Koss-Harnes et al. (2002) characterized the ultrastructural characteristics of EBS Ogna skin and found that blisters do not start via cytolysis of subnuclear central portions of the basal cell cytoplasm as in EBS Koebner and EBS Weber-Cockayne, but originate in the deepest areas of the basal cell cytoplasm, immediately above (but not within) hemidesmosomes. In unseparated perilesional and preblistering skin, keratin filaments are inconspicuous and normal for basal cells, but their insertion into the hemidesmosome attachment plates is impaired. Clumped basal keratins as in the Dowling-Meara type (131760) were not found in any of the skin samples. The hemidesmosomes themselves are normally structured with regard to their extracellular portions, but their intracellular attachment plates are mostly thin, their thickness being about half that of normal hemidesmosome attachment plates. This specific ultrastructure is significantly different from classical cases of EBS Koebner, EBS Weber-Cockayne, and EBS Dowling-Meara, all of which form entirely normal hemidesmosomes. Consistent with the absence of muscular symptoms in these patients, muscle biopsies from several affected members of the Norwegian kindred showed normal staining patterns using antibodies to plectin.

Mapping

Olaisen and Gedde-Dahl (1973) concluded that the locus for this disorder is closely linked (about 3 cM) to that for red cell soluble glutamate-pyruvate transaminase (GPT; 138200). Inasmuch as GPT has been localized to 8q24, EBS1 must be located there as well.

Molecular Genetics

Koss-Harnes et al. (2002) reported that the EBS Ogna phenotype is due to a site-specific heterozygous missense mutation within the rod domain of plectin (601282.0005). Mutations in plectin also cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (226670). Koss-Harnes et al. (2002) showed that EBS Ogna is not restricted to a single Norwegian kindred as theretofore believed. A German family with the phenotypic hallmarks of EBS Ogna carried an identical de novo mutation. Koss-Harnes et al. (2002) concluded that these 2 mutations arose about 200 years apart.