A heritable keratinization defect of the superficial epidermis in norfolk terriers.
ABSTRACT Although well-characterized in man, abnormal cornification secondary to heritable superficial keratin defects is rarely reported in animals. This report describes a mild cornification defect in seven related Norfolk terrier dogs. Lesions were present at birth and pedigree analysis suggested an autosomal recessive mode of inheritance. The affected dogs had hyperpigmented skin with scaling following mild trauma. The lesions were generalized but most prominent in the glabrous skin of the axillary and inguinal regions-areas where the epidermis is not protected by hair and is subject to frequent trauma. The most striking histological change was vacuolation in the upper epidermis, which often resulted in epidermolysis and blister formation. All of the affected dogs showed similar gross and histological changes. Ultrastructural changes included abnormal keratin filament clumping, prominent clear spaces in the cytoplasm of suprabasal keratinocytes, and abnormal keratohyaline granules. Immunohistochemical labelling for keratin 10 demonstrated a lack of expression in the superficial epidermis of affected dogs. All of the morphological changes noted in the Norfolk terriers were consistent with a mild form of a heritable defect in superficial keratin synthesis.
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ABSTRACT: Defective keratins are the cause of a number of hereditary disorders of the epidermis and other epithelia. The disease-causing mutations in keratins are clustered in the rod domain, and mutations in the helix boundary peptides cause the most severe forms of epidermal fragility syndromes. Siemens described a family with an atypical, mild form of bullous congenital ichthyosiform erythroderma. Linkage analysis in this family indicated that a defective type II keratin might be the underlying cause, keratins K1 and K2e being the best candidates. A substitution of valine for aspartic acid was detected at position 340 (D340V) in the L12 region of the K1 polypeptide. The mutation was found to cosegregate with the disorder in the family. Herewith, a genotype-phenotype correlation is shown for bullous congenital ichthyosiform erythroderma comparable with that described for epidermolysis bullosa simplex.Journal of Investigative Dermatology 01/1999; 111(6):1224-6. · 6.19 Impact Factor
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ABSTRACT: Ichthyosis bullosa of Siemens is a blistering disorder with autosomal dominant inheritance. The disease resembles bullous congenital ichthyosiform erythroderma but is less severe. Keratins K1 and K10 have been implicated in bullous congenital ichthyosiform erythroderma. Linkage analysis pointed to the involvement of a keratin type II gene (12q11-13) in ichthyosis bullosa of Siemens. Mutations in the highly conserved regions of K1, a member of the type II gene cluster, were excluded. The gene coding for keratin 2e is also located in the type II gene cluster and the expression of the gene coincides with the occurrence of epidermolytic hyperkeratosis. Sequence analysis revealed the presence of mutations in the K2e gene in patients with ichthyosis bullosa of Siemens. Three different mutations were detected, one in the 1A domain and two in the 2B domain of the rod. Furthermore, histologic and ultrastructural examination of skin biopsies indicated that ichthyosis exfoliativa is identical to ichthyosis bullosa of Siemens. This was confirmed by the results of the molecular analysis. In the family diagnosed as ichthyosis exfoliativa, a mutation was detected that was identical to the mutation found in one of the families with ichthyosis bullosa of Siemens.Journal of Investigative Dermatology 10/1994; 103(3):286-9. · 6.19 Impact Factor
- Experimental Dermatology - EXP DERMATOL. 01/1999; 8(6):501-503.