High-resolution array genomic hybridization in prenatal diagnosis

Array genomic hybridization (AGH) can detect chromosomal gains or losses that are 100 times smaller than those identifiable by conventional cytogenetic methods. Genome-wide AGH can identify genomic imbalance that causes birth defects and mental retardation at least twice as frequently as conventional cytogenetic analysis. Using AGH as a prenatal test for fetal genomic imbalance offers the promise of detecting pathogenic gain or loss of genomic material more quickly and much more frequently than current methods. However, the chance of finding a result of uncertain clinical significance is much greater than with conventional cytogenetic analysis, and the benefit–cost ratio of doing AGH in addition to conventional cytogenetic analysis in pregnancies at high risk for Down syndrome is likely to be poor. Very little is known about the natural history and range of clinical variability associated with most pathogenic submicroscopic copy number variants (CNVs). It seems doubtful that patients can be adequately counseled for prenatal AGH testing in most cases because the risks and benefits are unknown. At present, AGH should be offered for prenatal diagnosis only if the pregnancy is at especially high risk of having a pathogenic CNV or if AGH is being done as part of a clinical trial. Copyright © 2008 John Wiley & Sons, Ltd.     

Cytogenetic analysis of trophoblasts by comparative genomic hybridization in embryo-fetal development anomalies

Cytogenetic studies of spontaneous abortions or intrauterine fetal death depend on conventional tissue culturing and karyotyping. This technique has limitations such as culture failure and selective growth of maternal cells. Fluorescent in situ hybridization (FISH) using specific probes permits diagnosis of aneuploidies but is limited to one or a few chromosomal regions. Comparative genomic hybridization (CGH) provides an overview of chromosomal gains and losses in a single hybridization directly from DNA samples. In a prospective study, we analyzed by CGH trophoblast cells from 21 fetuses in cases of spontaneous abortions, intrauterine fetal death or polymalformed syndrome. Six numerical chromosomal abnormalities including one trisomy 7, one trisomy 10, three trisomies 18, one trisomy 21 and one monosomy X have been correctly identified by CGH. One structural abnormality of the long arm of chromosome 1 has been characterized by CGH. One triploidy and two balanced pericentromeric inversions of chromosome 9 have not been identified by CGH. Sexual chromosomal constitutions were concordant by both classical cytogenetic technique and CGH. Contribution of trophoblast analysis by CGH in embryo-fetal development anomalies is discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

A comparative study of microvillar enzyme activities in the prenatal diagnosis of cystic fibrosis

The potential of four enzyme-based analytical systems has been compared in the secondtrimester prenatal diagnosis of cystic fibrosis (CF). Direct activity measurements were made of γ-glutamyltranspeptidase (GGTP), aminopeptidase M (APM) and the intestinal isoenzyme of alkaline phosphatase (ALP). In the fourth system the proportions of total ALP inhibited by phenylalanine and homoarginine, respectively, were assessed. Each system was applied to amniotic fluid samples from 94 pregnancies with al in 4 risk of CF, divided into retrospective (36) and prospective (58) series. No system gave an absolute separation of affected from unaffected cases. Measurement of APM and intestinal ALP (phenylalanine-inhibitable ALP) gave a better detection rate for CF (35 of 41 cases, 85 per cent) than did measurement of GGTP (63 per cent) or assessment of ALP proportions (76 per cent). APM had a lower false positive rate (4 per cent) than intestinal ALP (8 per cent). For both the latter systems the detection rate of CF rose to 96 per cent (25 of 26), if gestations less than 17 weeks were excluded.