The development of chromosome-specific probes (CSP) and fluorescent in-situ hybridization (FISH) has allowed for very rapid identification of selected numerical abnormalities. We attempt here to determine, in principle, what percentage of abnormalities would be detectable if only CSP-FISH were performed without karyotype for prenatal diagnosis. A total of 146 128 consecutive karyotypes for prenatal diagnosis from eight centres in four countries for 5 years were compared with predicted detection if probes for chromosomes 13, 18, 21, X and Y were used, and assuming 100% detection efficiency. A total of 4163 abnormalities (2.85%) were found including 2889 (69. 4%) (trisomy 21, trisomy 18, trisomy 13, numerical sex chromosome abnormalities, and triploidies) which were considered detectable by FISH. Of these, 1274 were mosaics, translocations, deletions, inversions, rings, and markers which would not be considered detectable. CSP-FISH is a useful adjunct to karyotype for high risk situations, and may be appropriate in low risk screening, but should not be seen as a replacement for karyotype as too many structural chromosome abnormalities will be missed.

No abstract

To provide a means for the prenatal diagnosis of CGD, we combin ed a modified nitroblue tetrazolium (NBT) slide test with quina crine staining for Y chromosome fluorescence. Blood samples (1 ~1 ) are applied to glass slides and the adherent cells incubate with NBT and phorbol myristate acetate, an activator of oxidative metabolism. Resultant metabolic activity produces microscopically observable formazan particles in 99-100% of adult an 95-100% of fetal granulocytes (PMN), in 0-1% of PMN from 4 CGD patients, and in 18-53% of PMN from 3 obligate CGD carriers. Since placental venipuncture samples are often contaminated wit maternal blood, it is necessary to distinguish fetal and maternal cells in such mixtures. Quinacrine staining reveals a Ybody in 50-90% of male fetal PMN. Such identification of male F?.Nby Y-fluorescence allows detection and assessment of oxidative activity of CGD cells diluted 1:100 in maternal cells. Thus, the modified NBT slide test with quinacrine staining of blood obtained by placental venipuncture provides a method for the prenatal diagnosis of CGD in male fetuses at risk for the X linked or autosomal recessive forms of the disease. Analysis of the physical arrangement of globin genes in cellular DNA is now feasible. High molecular weight DNA is digested with site-specific restriction endonucleases, fractionated in agarose gels, and hybridized with radioactive complementary globin cDNA either in situ or after transfer to nitrocellulose filters. This techniquepermits direct, autoradiographic visualization of DNA fragments containing globin gene sequences in DNA isolated from normal individuals and those with hemoglobinopathies. Comparison of the hybridization patterns of different DNAs provides a convenient, sensitive system for the detection of globin gene deletions or rearrangements. Study of homozygous athalassemia (hydrops fetalis) DNA revealed complete absence of specific DNA fragments containing a globin sequences. The sensitivity and clarity of the visualization of this deletion indicate that this new approach will be especially useful in the prenatal detection of globin gene deletions or rearrangements in amniotic cell DNA of fetuses at risk for severe thalassemia syndromes.A NEW FAMILIAL . . DYSMORPHIC SYNDROME Dustan C. Osborn 1 1 1 0 &lch (Spon. by Richard B. Goldbloom), of Pediatrics, Halifax, N.S. of which show a constellation of features similar to, but distinct frnm t h~ qn-rall~d Nnnnan

The process of prenatal diagnosis is unique in that the diagnosis and prognosis are made without seeing the patient. 45,X/46,XY mosaicism presents a special problem in this regard. The phenotype of 45,X/46,XY postnatally diagnosed children (pediatric group) was compared to that of 6 fetuses who were diagnosed from 7,000 amniocenteses (prenatal group). These amniocenteses were performed primarily because of an increased risk of chromosome abnormality. The pediatric group (age birth-18 yr) were all phenotypically abnormal, although none were mentally retarded. Seven patients presented with ambiguous genitalia, while 2 had primary amenorrhea. Sexual assignment was changed in 2. Abnormalities included rudimentary phallus, urogenital sinus, hypospadias, undescended testes, and short stature. All 9 patients required at least one surgical procedure. In contrast, the prenatally diagnosed fetuses (ages 3 months to 3 1/2 yr) were all phenotypically normal males. Four were noted to have male genitalia on ultrasonography. Thus, the phenotype of 45,X/46,XY mosaicism in prenatally diagnosed fetuses can be markedly different from that of individuals diagnosed postnatally. This must be considered when counseling patients.