A chromosomally normal 37-year-old woman was referred for preimplantation genetic diagnosis after having several conceptuses with trisomy 21. Segregation of chromosome 21 was assessed in unfertilised meiosis II oocytes and preimplantation embryos from PGD cycles using fluorescent in situ hybridisation (FISH). Of 7 preimplantation embryos, 5 were chromosomally abnormal with 4 having trisomy 21 and one being tetraploid. Of 4 oocytes, 3 had an abnormal chromosomal constitution with either an extra chromosome 21 or an extra chromatid 21. In one oocyte an extra chromatid 21 was detected in both the metaphase II complement and the first polar body providing the first direct evidence of a maternal trisomic germ cell line. Moreover, this result shows that the extra chromosome 21 can precociously divide into its two chromatids at the first meiotic division.

from its regulation of CDK 2 in the nucleus. 9 Therefore, the role of p27 in the pathogenesis of myeloma requires further study.Lastly, the infrequent p57 methylation in patients with MM is similar to another study, which showed p57 methylation in only four (15.4%) of 26 myeloma patients. 10 Moreover, gene silencing associated with methylation was demonstrated in WL2 cell line, in which demethylation led to re-expression of p57 transcript.In conclusion, in contrast to frequent methylation of p15 and p16, both CKI members of the INK4 family, we showed the absence of p21 and p27 methylation and infrequent p57 methylation in 55 patients with MM. This is also consistent with the absence of p21 and p27 methylation, and the infrequent methylation of p57 in myeloma cell lines. Our data suggested that epigenetic dysregulation of the INK4 family, instead of the CIP/KIP family of CKI, is the predominant mechanism to abrogate negative regulation of the G 1 S cell cycle control in MM. This is consistent with recent data showing an essential role of CDK4 but not CDK2 in cell proliferation. Promoter hypermethylation of the cyclin-dependent kinase inhibitor (CDKI) gene p21WAF1/CIP1/SDI1 is rare in various lymphomas and carcinomas.

A study was carried out to evaluate congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a disease marker in a defined population with familial adenomatous polyposis (FAP). Indirect ophthalmoscopy was performed on 75 individuals from 25 known families with FAP, of whom 32 were known to be affected and 43 were at a 50 per cent prior risk of developing the disease. A further ten individuals from five families with hereditary non-polyposis colorectal cancer (HNPCC) were also tested. CHRPE was seen in 28 of the 32 affected individuals, 27 of whom met the criteria for a positive examination. Three individuals at risk of FAP also had positive examinations. Five individuals from the families with HNPCC also had CHRPE, although none met the criteria for a positive examination. Of four types of CHRPE analysed, one (small pigmented dots) was found to be more frequent in older family members (P = 0.012), suggesting that this type of lesion may proliferate with age. Compliance with ophthalmic screening was 97 per cent in families with FAP. Using a combined set of diagnostic criteria, CHRPE identified affected individuals with a specificity of at least 94 per cent and a sensitivity of 84 per cent. Results argue for a combined screening programme for FAP of DNA analysis, indirect ophthalmoscopy and bowel examination.

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