RESUMO
El síndrome de Netherton (SN) es una enfermedad autosómica recesiva, muy poco frecuente, que se caracteriza por la presencia de eritrodermia ictiosiforme congènita, anomalías capilares y manifestaciones atópicas. Este síndrome es consecuencia de una mutación recesiva en el gen SPINK5. Las manifestaciones del síndrome de SN varían considerablemente entre las personas que lo padecen. Aquí informamos el caso de un recién nacido que presentaba insuficiencia respiratoria grave, hipotermia y eritrodermia, al que se le diagnosticó SN, confirmado mediante pruebas genéticas moleculares.
Netherton syndrome (NS) is a rare, autosomal recessive disease characterized with congenital ichthyosiform erythroderma, hair abnormality and atopic manifestations. This syndrome is caused by recessive mutation in the SPINK5 gene. Disease manifestations vary considerably among NS individuals. We report a newborn presented with severe respiratory insufficiency, hypothermia and erythroderma, was diagnosed as having NS and confirmed with molecular genetic testing.
Assuntos
Humanos , Masculino , Recém-Nascido , Insuficiência Respiratória/etiologia , Eritrodermia Ictiosiforme Congênita/etiologia , Síndrome de Netherton/diagnóstico , Insuficiência Respiratória/genética , Eritrodermia Ictiosiforme Congênita/genética , Síndrome de Netherton/genética , Inibidor de Serinopeptidase do Tipo Kazal 5/genética , Hipotermia/etiologia , Hipotermia/genética , MutaçãoRESUMO
Netherton syndrome (NS) is a rare, autosomal recessive disease characterized with congenital ichthyosiform erythroderma, hair abnormality and atopic manifestations. This syndrome is caused by recessive mutation in the SPINK5 gene. Disease manifestations vary considerably among NS individuals. We report a newborn presented with severe respiratory insufficiency, hypothermia and erythroderma, was diagnosed as having NS and confirmed with molecular genetic testing.
El síndrome de Netherton (SN) es una enfermedad autosómica recesiva, muy poco frecuente, que se caracteriza por la presencia de eritrodermia ictiosiforme congénita, anomalías capilares y manifestaciones atópicas. Este síndrome es consecuencia de una mutación recesiva en el gen SPINK5. Las manifestaciones del síndrome de SN varían considerablemente entre las personas que lo padecen. Aquí informamos el caso de un recién nacido que presentaba insuficiencia respiratoria grave, hipotermia y eritrodermia, al que se le diagnosticó SN, confirmado mediante pruebas genéticas moleculares.
Assuntos
Eritrodermia Ictiosiforme Congênita/etiologia , Síndrome de Netherton/diagnóstico , Insuficiência Respiratória/etiologia , Humanos , Hipotermia/etiologia , Hipotermia/genética , Eritrodermia Ictiosiforme Congênita/genética , Recém-Nascido , Masculino , Mutação , Síndrome de Netherton/genética , Insuficiência Respiratória/genética , Inibidor de Serinopeptidase do Tipo Kazal 5/genéticaRESUMO
Neutral lipid storage disease with ichthyosis (NLSDI; Chanarin-Dorfman syndrome) is an ichthyosiform syndrome, often associated with mutations in a lipid hydrolase, CGI-58. The presence of oil red O-positive, neutral lipid droplets in tissue biopsies, and/or in leukocytes on blood smears, coupled with a constellation of multisystem abnormalities and a pruritic ichthyosiform erythroderma, are together diagnostic of NLSDI. We investigated the pathogenesis of the ichthyosiform erythroderma in patients from three unrelated kindreds with a clinical diagnosis of NLSDI. Basal permeability barrier function and stratum corneum (SC) integrity were abnormal, but barrier recovery rates were faster than normal, as in atopic dermatitis. The basal barrier abnormality was linked to the secretion of lipid micro-inclusions, first segregated within lamellar bodies (LB), which then form a non-lamellar phase within the SC interstices, shown by combined ruthenium tetroxide post-fixation and lipid-retaining resin-white embedding. With colloidal lanthanum nitrate perfusion, excess water/solute movement was restricted to the SC interstices, and further localized to non-lamellar domains. Phase separation of excess stored lipid provides a unifying pathogenic mechanism not only for NLSDI, but also in several other inherited ichthyosiform disorders of lipid metabolism, such as recessive X-linked ichthyosis and type 2 Gaucher's disease.
Assuntos
Eritrodermia Ictiosiforme Congênita/etiologia , Eritrodermia Ictiosiforme Congênita/patologia , Erros Inatos do Metabolismo Lipídico/etiologia , Erros Inatos do Metabolismo Lipídico/patologia , 1-Acilglicerol-3-Fosfato O-Aciltransferase , Adulto , Criança , Epiderme/patologia , Epiderme/ultraestrutura , Esterases/genética , Saúde da Família , Feminino , Humanos , Eritrodermia Ictiosiforme Congênita/genética , Corpos de Inclusão/patologia , Corpos de Inclusão/ultraestrutura , Lipase/genética , Metabolismo dos Lipídeos , Erros Inatos do Metabolismo Lipídico/genética , Microscopia Eletrônica , Permeabilidade , Síndrome , Água/metabolismoAssuntos
Anormalidades Múltiplas , Eritrodermia Ictiosiforme Congênita , Deformidades Congênitas dos Membros , Anormalidades Múltiplas/etiologia , Anormalidades Múltiplas/fisiopatologia , Encéfalo/anormalidades , Diagnóstico Diferencial , Feminino , Ligação Genética/genética , Humanos , Eritrodermia Ictiosiforme Congênita/etiologia , Eritrodermia Ictiosiforme Congênita/fisiopatologia , Deformidades Congênitas dos Membros/etiologia , Deformidades Congênitas dos Membros/fisiopatologia , Prognóstico , Síndrome , Cromossomo X/genéticaRESUMO
Epidermolytic hyperkeratosis (EH) is a skin disease characterized by keratin filament clumping and degeneration in terminally differentiating epidermal cells. We have discovered that the genetic basis for EH resides in mutations in differentiation-specific keratins. Two of six distinct incidences of EH had a keratin 10 (K10) point mutation in a highly conserved arginine. Remarkably, this same residue is mutated in the basal epidermal K14 in three incidences of another skin disease, epidermolysis bullosa simplex (EBS). By genetic engineering, gene transfection, and 10 nm filament assembly, we show that this mutation is functionally responsible for the keratin filament clumping that occurs in basal (EBS) or suprabasal (EH) cells. These studies strengthen the link between filament perturbations, cell fragility, and degeneration first established with EBS. They also suggest a correlation between filament disorganization and either cytokinesis or nuclear shape, giving rise to the seemingly binucleate cells typical of EH.
Assuntos
Epidermólise Bolhosa Simples/genética , Eritrodermia Ictiosiforme Congênita/genética , Queratinócitos/metabolismo , Queratinas/genética , Sequência de Aminoácidos , Sequência de Bases , Diferenciação Celular , Células Cultivadas , Epidermólise Bolhosa Simples/patologia , Engenharia Genética , Humanos , Eritrodermia Ictiosiforme Congênita/etiologia , Eritrodermia Ictiosiforme Congênita/patologia , Filamentos Intermediários/metabolismo , Filamentos Intermediários/ultraestrutura , Queratinócitos/ultraestrutura , Dados de Sequência Molecular , Mutagênese Sítio-DirigidaRESUMO
Epidermolytic hyperkeratosis is an autosomal dominant disorder affecting the structural integrity of the suprabasal layers of human epidermis. We have recently documented in one family linkage of the disease phenotype to the cluster of type II keratins. We have now identified a leucine----proline amino acid substitution in the conserved H1 subdomain of keratin 1 that is present only in affected family members. Using a quantitative assay and electron microscopy with synthetic peptides, we show that, whereas the wild-type H1 peptide rapidly disassembles preformed keratin filaments in vitro, the mutant peptide does this far less efficiently. Therefore the mutation in keratin 1 is likely to cause defective keratin filaments and hence a defective cytoskeleton in the epidermal cells in vivo.
