We report the clinical and chromosomal findings in 8 patients with deletions of the long arm of chromosome 4. Four of these patients appear to have terminal deletions beginning in band 4q31, and therefore, lack the digital 1/3 of the long arm of chromosome 4. We confirm that deletion of 4q31 leads to qter causes a recognizable syndrome, and we further define the phenotype of that syndrome. A 5th patient has a horter terminal deletion, ie, 4q33 leads to qter. This deletion causes a milder phenotypic expression than that seen in the severe 4q terminal-deletion syndrome. The remaining 3 patients have interstitial deletions of the long arm of the 4th chromosome, including segments 4q21.1 leads to q25, 4q21.3 leads to q26, and 4q27 leads to q31.3. The phenotypic expression noted in these patients is variable in differs from the 4q terminal-deletion syndrome.

We analyzed 3000 consecutive amniocenteses for prenatal diagnosis to assess the frequency of abnormalities, safety of the procedure, technical and interpretive difficulties and overall diagnostic accuracy. Chromosomal abnormalities were detected in 2.4 per cent of the 2404 pregnancies tested because of advanced maternal age (greater than or equal to 35 years), in 1.2 per cent of 240 monitored because of prior trisomy 21 and in 9.1 per cent of 55 examined for other cytogenetic indications. Mosaicism was detected in 0.4 per cent, and unexpected translocations in 0.4 per cent. Amniotic fluid was obtained on the first attempt in 99.3 per cent of the last 1000 cases, and cultures established from 99.7 per cent of patients attending our clinic. The fluid was discolored in 1.2 per cent of patients, a quarter of whom had missed abortions. The rate of spontaneous abortion after amniocentesis was 1.5 per cent. There were 14 diagnostic errors, six serious enough to affect the outcome of pregnancy. The karyotyping error rate was 0.07 per cent. We conclude that prenatal diagnosis is safe, highly reliable and extremely accurate.

Of nine studies in vitro, six have indicated some degree of induced chromosomal breakage after exposure to LSD; three failed to confirm these results. The damage, when found, was generally of the chromatid type, arising during or after DNA synthesis. This damage, with one exception, was the result of concentrations of drug and durations of exposure which could not be achieved in humans with reasonable dosages. There did not appear to be a dose-response relation. The magnitude of damage, when found, was in the range encompassing the effects of many commonly used substances. The absence in vitro of excretory and detoxifying systems present in vivo, as well as several negative reports, cast doubt on the relevance of in vitro results. In 21 chromosomal studies in vivo, 310 subjects were examined. Of these, 126 were treated with pure LSD; the other 184 were exposed to illicit, "alleged" LSD. A maximum of only 18 of 126 (14.29 percent) of the subjects in the group exposed to pure LSD showed higher frequency of chromosome aberration than the controls. In contrast, a maximum of 90 of 184 (48.91 percent) of the subjects taking illicit LSD showed an increase in frequency of aberrations. Of all the subjects reported to have chromosome damage, only 18 of the 108 (16.67 percent) were exposed to pure LSD. The frequency of individuals with chromosomal damage reported among illicit drug users was more than triple that associated with the use of pharmacologically pure LSD. We conclude that chromosome damage, when found, was related to the effects of drug abuse in general and not, as initially reported, to LSD alone. We believe that pure LSD ingested in moderate dosages does not produce chromosome damage detectable by available methods. No significant work on carcinogenic potential of LSD has been reported so far. No cause-and-effect relation and no increase in the incidence of neoplasia among LSD users have been demonstrated. Case reports (three in 4.0 years) of leukemia and other neoplasia in this population are rare. The results of early chromosome studies suggested that true genetic damage might be a consequence of LSD exposure. The comprehensive evidence from studies on drosophila indicates no mutagenic effect from 0.28 to 500 microg of LSD per milliliter and a definite mutagenic effect from 2,000 to 10,000 microg/ml; this is consistent with a threshold response or a sigmoid dose-effect relation. We believe that LSD is, in fact, a weak mutagen, effective only in extremely high doses; it is unlikely to be mutagenic in any concentration used by human subjects. Circular dichroism experiments suggested that the specific mechanism of action of LSD on DNA may be a direct interaction resulting in conformational changes in the DNA helix. These changes are unlikely to result in a decrease of internal stability sufficient to cause breakage of chromosomes, but they may be the physical basis of the weak mutagenicity. Early chromosomal studies implicated LSD as a potential cause of congenital malformations, fetal wastage, and germinal chr...

SUMMARY Retinoblastoma occurs with increased frequency in children born with a deletion of the long arm of chromosome 13. Recent reviews have noted that the region 13q14 is consistently deleted in documented cases. Prometaphase and late prophase banding allowed Yunis and Ramsay' to determine that a deletion in one patient included the sub-bands q14 12, q14 13, and q14-2, and a portion of q14 11 and q14-3. We report the results of similar cytogenetic techniques applied in the case of a 26 month old Caucasian female with unilateral retinoblastoma, moderate developmental delay, and subtle dysmorphology.

This report describes a family in which eight individuals in three generations had mental retardation in association with a characteristic pattern of clinical problems and physical abnormalities including short stature, eczema, hernias, delayed puberty, dysmorphic facies and digital anomalies. The family history was consistent with a chromosomal rearrangement with transmission through balanced carriers. Routine ASG banding studies showed extra chromosomal material on a chromosome 16 but failed to demonstrate any differences between the affected individuals and the presumed carriers. However, subsequent studies utilizing trypsin banding and microspectrophotometry of individual chromosomes demonstrated that the affected individuals were partially trisomic for the distal band of the long arm of chromosome 5 and that 0.273 units of a chromosome 5 were translocated to chromosome 16. This definitive cytogenetic diagnosis permitted accurate prenatal diagnosis to be carried out on the fetus of a balanced carrier female. The application of these techniques to previously obscure familial dysmorphic syndromes is recommended.