RESUMEN
This paper describes a novel genetic defect which causes fish-eye disease in four homozygous probands and its biochemical presentation in 34 heterozygous siblings. The male index patient presented with premature coronary artery disease, corneal opacification, HDL deficiency, and a near total loss of plasma lecithin:cholesterol acyltransferase (LCAT) activity. Sequencing of the LCAT gene revealed homozygosity for a novel missense mutation resulting in an Asp131 - Asn (N131D) substitution. Heterozygotes showed a highly significant reduction of HDL-cholesterol and apolipoprotein A-I levels as compared with controls which was associated with a specific decrease of LpA-I:A-II particles. Functional assessment of this mutation revealed loss of specific activity of recombinant LCAT(N131D) against proteoliposomes. Unlike other mutations causing fish-eye disease, recombinant LCAT(N131D) also showed a 75% reduction in specific activity against LDL. These unique biochemical characteristics reveal the heterogeneity of phenotypic expression of LCAT gene defects within a range specified by complete loss of LCAT activity and the specific loss of activity against HDL. The impact of this mutation on HDL levels and HDL subclass distribution may be related to the premature coronary artery disease observed in the male probands.
Asunto(s)
Deficiencia de la Lecitina Colesterol Aciltransferasa/genética , Lipoproteínas HDL/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Mutación Puntual , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Apolipoproteína A-I/sangre , Asparagina , Ácido Aspártico , Secuencia de Bases , HDL-Colesterol/sangre , Cartilla de ADN , Tamización de Portadores Genéticos , Homocigoto , Humanos , Lipoproteína(a)/análogos & derivados , Lipoproteína(a)/sangre , Lipoproteínas HDL/sangre , Lipoproteínas HDL/deficiencia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fenotipo , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Reacción en Cadena de la Polimerasa , Valores de Referencia , Mapeo RestrictivoRESUMEN
The total phospholipid content of the supernatant fluid decreases rapidly with increasing relative centrifugal force when amniotic fluid is centrifuged. Possible explanations for this are discussed. The effect of storage on the total phospholipid content of amniotic fluid at different temperatures and the influence of contamination with blood and meconium are also described.
Asunto(s)
Líquido Amniótico/análisis , Fosfolípidos/análisis , Sangre , Recuento de Células , Centrifugación , Femenino , Humanos , Recién Nacido , Meconio/análisis , Embarazo , Manejo de Especímenes , TemperaturaRESUMEN
The circadian rhythm in the urinary excretion of etiocholanolone, of androsterone and of dehydroepiandrosterone in normal menstruating women was studied. The excretion patterns of etiocholanolone and androsterone seem to be nearly synchronous, but not equal, thus resulting in a diurnal variation.