Ucsf macvector skin#

Ucsf macvector skin#

BCIE is characterized by the presence of erythroderma and skin blistering at birth, later replaced by a diffuse hyperkeratosis of the skin and, by the presence of palmoplantar keratoderma (PPK). Bullous congenital ichthyosiform erythroderma (BCIE, OMIM 113800), also known as epidermolytic hyperkeratosis (EH) and now classified inside the class of Keratinopatic Ichthyoses, is an autosomal dominant disorder of the skin associated to mutations in KRT1 and KRT10 genes. The resulting phenotype is generally characterized by the type, the localization and the role of the protein involved. These genetic defects often lead to incorrect interaction among the basic components of the intermediate filament (IF) network, generating an incomplete or abnormal cytoskeleton. Several mutations have been found in genes coding for structural epidermal protein keratins, involved in epidermal differentiation and maintenance. Molecular genetic defects of several inherited skin diseases (Genodermatosis) have been characterized in the last decades. Moreover, this is a further demonstration of the presence of somatic mutations arising in later stages of the embryogenesis, generating a mosaic phenotype. These data demonstrate once again the importance of the head domain (V1) of K1 in the formation of a functional keratinocyte cytoskeleton. The mutation taster in silico analysis also returned a high probability for a deleterious mutation.

Moreover, a computational analysis of the wild-type and V1-mutated K1/K10 keratin dimers, suggests an unusual interaction between these keratin filaments. The deleted sequence involves the ISIS subdomain, containing a lysine residue already described as fundamental for epidermal transglutaminases in the crosslinking of IF cytoskeleton. These results suggest a somatic mutation causing an alteration in K1 N-terminal variable domain (V1). DNA extracted from peripheral blood lymphocytes did not display the presence of the mutation. Genetic analysis performed demonstrates the heterozygous deletion NM_006121.4:r.274_472del for a total of 198 nucleotides, in KRT1 cDNA obtained by a palmar lesional skin biopsy, corresponding to the protein mutation NP_006112.3:p.Gly71_Gly137del. Light and confocal histological analysis confirmed the presence of epidermolityic hyperkeratosis. No other relatives of the patient showed any dermatological disease. We evaluated a patient presenting hyperkeratosis localized monolaterally in the right palmar area, characterized by linear yellowish hyperkeratotic lesions following the Blaschko lines. Cases of mosaicism in PPKs due to somatic keratin mutations have also been described in scientific literature. Specific mutations of keratin 16 (K16) and keratin 1 (K1) have been associated to EPPK, and NEPPK. PPKs can be epidermolytic (EPPK) or non epidermolytic (NEPPK). Palmoplantar keratodermas (PPKs) are characterized by thickness of stratum corneum and epidermal hyperkeratosis localized in palms and soles.