Prenatal and postnatal characterization of Y chromosome structural anomalies by molecular cytogenetic analysis

We describe three cases in which we used fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and comparative genomic hybridization (CGH) to characterize Y chromosome structural anomalies, unidentifiable by conventional G-banding. Case 1 was a 46,X,+mar karyotype; FISH analysis revealed an entire marker chromosome highlighted after hybridization with the Y chromosome painting probe. The PCR study showed the presence of Y chromosome markers AMG and SY620 and the absence of SY143, SY254 and SY147. CGH results confirmed the loss of Yq11.2-qter. These results indicated the presence of a deletion: del(Y)(q11.2). Case 2 was a 45,X [14]/46,XY[86] karyotype with a very small Y chromosome. The PCR study showed the presence of Y chromosome markers SY620 and AMG, and the absence of SY143, SY254 and SY147. CGH results showed gain of Yq11.2-pter and loss of Yq11.2-q12. These results show the presence of a Yp isodicentric: idic(Y)(q11.2). Case 3 was a 45,X,inv(9)(p11q12)[30]/46,X,idic(Y)(p11.3?),inv(9)(p11q12)[70] karyotype. The FISH signal covered all the abnormal Y chromosome using a Y chromosome paint. The PCR study showed the presence of Y chromosome markers AMG, SY620, SY143, SY254 and SY147. CGH only showed gain of Yq11.2-qter. These results support the presence of an unbalanced (Y;Y) translocation. Our results show that the combined use of molecular and classical cytogenetic methods in clinical diagnosis may allow a better delineation of the chromosome regions implicated in specific clinical disorders. Copyright © 2002 John Wiley & Sons, Ltd.     

An increase in cost-effectiveness of first trimester maternal screening programmes for fetal chromosome anomalies is obtained by contingent testing

We assessed the discriminatory efficiency and cost-effectiveness of a novel way of organising first trimester screening for Down syndrome (DS), contingent testing, where a serological test (PAPP-A and β-hCG: the double test) is made in early first trimester and followed by nuchal translucency testing (NT) only in women with an intermediate risk, e.g. <1:65 and >1:1000, and not in all women as in normal first trimester screening (NFTS). Using Monte Carlo simulation contingent testing had a detection rate (DR) of 78.9% and a false-positive rate (FPR) of 4.0% for DS with 19.4% of women offered NT testing. The DR of NFTS was 85.5% and the FPR 4.4%. The decrease in NT screening was associated with an increase from 23% to 29% in the proportion of DS cases born. The cost of the contingent testing programme was £53 000 per DS case not born and £91 000 in NFTS. The number of aborted fetuses per DS case were 0.35 and 0.36, respectively. Thus, contingent testing is an organisation of first trimester screening where costs can be reduced with a marginal decrease in performance. Contingent testing is attractive in areas where NT screening is the bottleneck preventing the introduction of first trimester screening. Copyright © 2002 John Wiley & Sons, Ltd.