Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermolytic hyperkeratosis is caused by mutations of the differentiation-specific keratins K1 and K10. These mutations produce a weakened cytoskeleton that is prone to collapse resulting in cell fragility and lysis. In this study we have analyzed cultured keratinocytes from EHK patients bearing 10R-to-H and 15L-to-S mutations within the 1A segment of the K10 rod domain. Keratinocytes were grown submerged in serum-free medium and induced to differentiate by growing to confluence and increasing the Ca++ concentration in the medium. Cultures were either harvested for mRNA sequence analysis or subjected to immunofluorescence microscopy. Differentiating keratinocytes from these patients were found to express these K10 mutations in their mRNA. Moreover, these cells could be distinguished from normal keratinocytes by their aberrant morphology. EHK keratinocytes frequently exhibited a collapsed perinuclear network of K1/K10 filaments and sometimes peripheral granules of K1 and K10 aggregates, reminiscent of the cells of the suprabasal layers in these patients. This report documents the expression of mutant keratin 10 in cultured EHK keratinocytes.
 ...
PMID:Abnormal keratin 1 and 10 cytoskeleton in cultured keratinocytes from epidermolytic hyperkeratosis caused by keratin 10 mutations. 751 36

Epidermolytic hyperkeratosis (EHK) is a congenital, autosomal dominant disorder of cornification characterized by hyperkeratosis and blister formation. The clinical manifestations are heterogeneous, with respect to the extent of body surface involvement, palmar and plantar hyperkeratosis and the presence of erythroderma. Point mutations in the genes encoding the suprabasal-specific keratins, keratins 1 and 10 have been identified in EHK patients. The inappropriate amino acid substitutions cause a collapse of the keratin filament network, resulting in cytolysis of the involved keratinocytes. We report a severe case of EHK with a single base pair mutation that causes a threonine for asparagine substitution in residue 8 (N8T) of the 1A region of the keratin 1 protein. This is the region involved in molecular overlaps between neighboring keratin heterodimers. These findings suggest that even conservative amino acid substitutions in overlap regions can cause tonofilament clumping.
 ...
PMID:An asparagine to threonine substitution in the 1A domain of keratin 1: a novel mutation that causes epidermolytic hyperkeratosis. 1023 3

Epidermolytic hyperkeratosis (EH) in man is a complex of congenital, ichthyosiform skin diseases characterized clinically by blistering and hyperkeratosis. These clinical signs are the result of a collapse of the cytoskeleton, seen ultrastructurally as tonofilament clumping and cytolysis within terminally differentiating epidermal cells. In man, specific mutations in keratin 1, 2e, 9 or 10 underlie the various types of EH. This report describes the clinical, histopathological, immunohistochemical and ultrastructural findings in a 6-month-old dog with severe multifocal hyperkeratosis. The morphological changes were comparable with those of EH in man, indicating that this disease, presumably with a similar underlying pathogenetic mechanism, also occurs in the dog.
 ...
PMID:Epidermolytic ichthyosis in a dog: clinical, histopathological, immunohistochemical and ultrastructural findings. 1080 85