RESUMEN
OBJECTIVE: We sought to evaluate performance of a noninvasive prenatal test for fetal trisomy 21 (T21) and trisomy 18 (T18). STUDY DESIGN: A multicenter cohort study was performed whereby cell-free DNA from maternal plasma was analyzed. Chromosome-selective sequencing on chromosomes 21 and 18 was performed with reporting of an aneuploidy risk (High Risk or Low Risk) for each subject. RESULTS: Of the 81 T21 cases, all were classified as High Risk for T21 and there was 1 false-positive result among the 2888 normal cases, for a sensitivity of 100% (95% confidence interval [CI], 95.5-100%) and a false-positive rate of 0.03% (95% CI, 0.002-0.20%). Of the 38 T18 cases, 37 were classified as High Risk and there were 2 false-positive results among the 2888 normal cases, for a sensitivity of 97.4% (95% CI, 86.5-99.9%) and a false-positive rate of 0.07% (95% CI, 0.02-0.25%). CONCLUSION: Chromosome-selective sequencing of cell-free DNA and application of an individualized risk algorithm is effective in the detection of fetal T21 and T18.
Asunto(s)
ADN/sangre , Síndrome de Down/diagnóstico , Diagnóstico Prenatal/métodos , Trisomía/diagnóstico , Adolescente , Adulto , Algoritmos , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 21/genética , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Trisomía/genética , Adulto JovenRESUMEN
Arginase I (AI) has a critical function in mammalian liver as the final enzyme in the urea cycle responsible for the disposal of ammonia from protein catabolism. AI is also expressed in various extrahepatic tissues and may play a role in regulating arginine levels and in providing ornithine for biosynthetic reactions that generate various critical intermediary metabolites such as glutamate, glutamine, GABA, agmatine, polyamines, creatine, proline, and nitric oxide. AI is expressed in red blood cells (RBCs) only in humans and certain higher primates. Macaca fascicularis has been identified as an evolutionary transition species in which RBC-AI expression is co-dominantly regulated. The M. fascicularis AI gene was analyzed to understand AI expression in erythrocytes. Erythroid progenitor cells [nucleated red blood cells (nRBCs)] isolated from cord blood were utilized to demonstrate AI expression by immunocytochemical staining using anti-AI antibody. Introduction of EGFP reporter vectors into nRBC showed that the proximal 1.2 kbp upstream of the AI gene is sufficient for AI expression. Expression of a second arginase isoform, AII, in nRBCs was discovered by cDNA profiling. This contrasts with mature fetal or adult RBCs which contain only the AI protein. In addition, an alternatively spliced AI (AI(')) variant was observed from erythroid mRNA analysis with an alternative splice acceptor site located within intron 2, causing the insertion of eight additional amino acids yet retaining significant enzymatic activity.