RESUMO
Desmosomes are intercellular adhesive junctions and attachment sites for the intermediate filament (IF) cytoskeleton, prominent in tissues subject to high levels of mechanical stress such as the epidermis and heart. The obligate desmosomal constituent, plakoglobin (PG), is involved in coupling transmembrane desmosomal components with IFs. PG also contributes to intercellular adhesion through adherens junctions and has additional signaling roles. To date, two mutations in the gene encoding PG, JUP, have been described, and in both instances, patients harboring pathogenic mutations suffered from arrhythmogenic right ventricular cardiomyopathy with or without skin abnormalities. We describe homozygous nonsense mutation, p.S24X, and homozygous splice site mutation, c.468G>A, in the JUP gene that results in skin fragility, diffuse palmoplantar keratoderma, and woolly hair with no symptoms of cardiomyopathy. We show barely detectable levels of PG immunostaining in skin sections from patients harboring these mutations and show that an alternative AUG codon in p.S24X mRNA translates a 42-amino-acid N-terminal truncation. We conclude that PG is required for correct maintenance of skin integrity, and the absence of heart phenotype in patients suggests that aberrant PG expression does not compromise normal human heart development in children. Our findings provide new insight into the distinct roles that PG has in the epidermis and heart.
Assuntos
Cardiomiopatias/genética , Códon sem Sentido/genética , Desmoplaquinas/genética , Coração/crescimento & desenvolvimento , Homozigoto , Sítios de Splice de RNA/genética , Dermatopatias Genéticas/genética , Biópsia , Cardiomiopatias/fisiopatologia , Criança , Pré-Escolar , DNA Complementar/genética , Desmoplaquinas/fisiologia , Feminino , Coração/fisiologia , Humanos , Lactente , Masculino , Técnicas de Amplificação de Ácido Nucleico , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , Pele/patologia , Pele/ultraestrutura , Dermatopatias Genéticas/fisiopatologia , gama CateninaRESUMO
We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.
Assuntos
Tecido Conjuntivo/ultraestrutura , Hipoplasia Dérmica Focal/ultraestrutura , Adipócitos/metabolismo , Adipócitos/ultraestrutura , Adolescente , Biomarcadores/metabolismo , Criança , Colágeno/metabolismo , Colágeno/ultraestrutura , Tecido Conjuntivo/metabolismo , Tecido Elástico/metabolismo , Tecido Elástico/ultraestrutura , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestrutura , Feminino , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Hipoplasia Dérmica Focal/metabolismo , Humanos , Técnicas Imunoenzimáticas , Microscopia Eletrônica de Transmissão , Reação do Ácido Periódico de SchiffRESUMO
We report a family in which geroderma osteodysplastica affected two male siblings. They showed the characteristic features associated with this syndrome: a prematurely aged face with wrinkly, lax skin, more prominent on the acral regions, associated with joint laxity, osteoporosis, and skeletal abnormalities. The main histologic abnormalities were fragmented elastic fibers that were diminished in number. Although collagen fibers showed changes in their orientation, they were normal in structure and number. We consider the differential diagnosis with other syndromes associated with cutis laxa using clinical, radiologic, and histopathologic criteria.
Assuntos
Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/patologia , Cútis Laxa/genética , Cútis Laxa/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Linhagem , SíndromeRESUMO
Two siblings with familial cutaneous collagenoma syndrome had the essential clinical features of multiple skin-colored nodules on the trunk and upper arms. On light microscopy, histopathologic findings included excessive accumulation of dense, coarse collagen in the dermis. Elastic tissue stains demonstrated a proportionately diminished number of abnormal elastic fibers intermingled with the collagen bundles. A predominance of densely packed collagen bundles of normal morphology with a marked decrease in abnormal elastic tissue were the major ultrastructural features. The diagnosis was therefore confirmed to be connective tissue nevi of the collagen type. The differential diagnosis of connective tissue nevi disorders is delineated.
Assuntos
Doenças do Tecido Conjuntivo/patologia , Dermatopatias/patologia , Criança , Doenças do Tecido Conjuntivo/genética , Diagnóstico Diferencial , Hamartoma/patologia , Humanos , MasculinoRESUMO
Niña de 10 años de edad, de raza indo-americana, con placas verrugosas orales de siete meses de evolución. El diagnóstico clínico de hiperplasia epitelial focal fue confirmado por microscopía electrónica. Se realiza la descripción de esta patología frecuente en comunidades indígenas de bajo nivel socioeconómico y su diagnóstico diferencial con otras patologías orales clínicamente similares (AU)
Assuntos
Humanos , Feminino , Hiperplasia Epitelial Focal/diagnóstico , Hiperplasia Epitelial Focal/patologia , Hiperplasia Epitelial Focal/terapia , Gelo-Seco/uso terapêuticoRESUMO
Niña de 10 años de edad, de raza indo-americana, con placas verrugosas orales de siete meses de evolución. El diagnóstico clínico de hiperplasia epitelial focal fue confirmado por microscopía electrónica. Se realiza la descripción de esta patología frecuente en comunidades indígenas de bajo nivel socioeconómico y su diagnóstico diferencial con otras patologías orales clínicamente similares