RESUMO
Opitz-Kaveggia syndrome is a rare X-linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty-three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz-Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.
Assuntos
Complexo Mediador/genética , Mutação , Síndrome Acrocalosal/genética , Adolescente , Agenesia do Corpo Caloso , Sequência de Aminoácidos , Anus Imperfurado/genética , Constipação Intestinal/genética , Humanos , Lactente , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/genética , Dados de Sequência Molecular , Hipotonia Muscular/congênito , Hipotonia Muscular/genética , Linhagem , Alinhamento de SequênciaRESUMO
Human monocytes express two types of IgG FcR, Fc gamma RI and Fc gamma RII. These can be assayed by using indicator E sensitized by human IgG (EA-human IgG) or mouse IgG1, (EA-mouse IgG1), respectively. On mouse macrophages, Fc gamma RI is sensitive to trypsin, whereas Fc gamma RII is trypsin resistant. We studied the effects of the proteolytic enzymes pronase and trypsin on human monocyte Fc gamma R. Neither enzyme caused a decrease in rosetting mediated by monocyte Fc gamma RI. Human Fc gamma RII is polymorphic, and monocytes interact either strongly or weakly with mouse IgG1. The interaction of low responder monocytes with mouse IgG1 was dramatically increased (to the level exhibited by high responder monocytes) by protease treatment. The effects of proteases on Fc gamma RII were investigated in more detail by using monocytes from which Fc gamma RI was selectively modulated by using immobilized immune complexes. Proteolysis of such modulated monocytes induced an increased interaction with EA-human IgG. Fc gamma RII appears to mediate this interaction. This conclusion is supported by the observation that after proteolysis, the Fc gamma RII-mediated binding of EA-mouse IgG1 becomes susceptible to inhibition by (monomeric) human IgG. To quantify the effect of proteolytic enzymes on Fc gamma RII, we performed binding studies with cell line K562, that expresses only Fc gamma RII. A significant increase in Ka of Fc gamma RII for dimeric human IgG complexes was observed when K562 cells were treated with protease. To elucidate the mechanism of this enhancement of Ka by proteolysis, we performed immunoprecipitation studies. Neither m.w., nor IEF pattern of Fc gamma RII were influenced by proteolysis. Moreover, the expression of Fc gamma RII was not affected by proteolysis as evidenced by immunofluorescence studies and Scatchard analysis, and neither were Fc gamma RI or Fc gamma RIII induced. We conclude that proteolysis increases the affinity of Fc gamma RII for human IgG, and speculate that such a proteolysis-induced change may also occur in vivo, e.g., at inflammatory sites.
Assuntos
Afinidade de Anticorpos , Antígenos de Diferenciação/metabolismo , Imunoglobulina G/metabolismo , Monócitos/metabolismo , Peptídeo Hidrolases , Receptores Fc/metabolismo , Citotoxicidade Celular Dependente de Anticorpos , Antígenos de Diferenciação/isolamento & purificação , Sítios de Ligação de Anticorpos , Linhagem Celular , Eritrócitos/imunologia , Eritrócitos/metabolismo , Humanos , Hidrólise , Focalização Isoelétrica , Leucemia Eritroblástica Aguda/metabolismo , Substâncias Macromoleculares , Peso Molecular , Receptores Fc/isolamento & purificação , Receptores de IgG , Formação de RosetaRESUMO
In order to investigate the effect of a CO2 laser on dental tissues, 51 healthy human teeth were lased and prepared for macroscopic, histological and SEM examination using standardized methods. The alterations induced by the thermic shock varied according to the tissue's composition and the lasing's intensity. The effects generally appeared as cracks with fragmentation of the superficial enamel, and a carbonization of the cavity. The underlying pulp showed a disintegration of the odontoblastic layer and an oedema, the severity of which depended on the residual dentinal thickness and the lasing's intensity. The study's results, divergent from those often found promising in the abundant literature, bring to light the biological incompatibility of this type of hard laser regarding the dental organ and suggest caution concerning eventual therapeutic indications.