Clinical findings in a family with familial adenomatous polyposis and a missense mutation of the adenomatous polyposis coli gene.

BACKGROUND: More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function. METHODS: In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band. RESULTS: A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects. CONCLUSIONS: In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.

Cost-effectiveness ratio of chorionic villi biopsy for the prenatal diagnosis of chromosomal aberrations as compared with amniocentesis.

The observed cost of amniocentesis for the prenatal diagnosis of chromosomal aberrations in pregnancies at risk because of advanced maternal age was compared with the estimated cost of chorionic villi biopsy (CVB). The cost of CVB was estimated to be 22% less than that of amniocentesis when the cost of the sampling procedure, the laboratory charges and the cost of spontaneous and therapeutic abortions were considered.

Prenatal diagnosis of fragile X in a heterozygous female fetus and postnatal follow-up.

An apparently normal female infant was born after the prenatal diagnosis of fragile Xq27-28 present in about 4 per cent of amniocytes . The mildly retarded mother had been found in early pregnancy to be heterozygous for fragile X. The child, now 9 months old, showed about the same level of fragile X expression as her mother. Variations in the proportion of cells with fragile X appeared to be related to cell type and laboratory techniques. The infant's growth and development have been normal. Different techniques to induce or increase the expression of fragile X are discussed.

An in vitro and in vivo study of a BrdU-sensitive fragile site in the Chinese hamster.

The frequencies of chromosome aberrations and development of the bromodeoxyuridine (BrdU)-sensitive fragile site were studied in vitro in Chinese hamster kidney and bone marrow cells and in vivo in Chinese hamster bone marrow cells. Chromosome aberrations in these cell systems were measured in response to different concentrations of BrdU, fluorodeoxyuridine, or both. The fragile site was found in both homologues of chromosome 1 at 1q22. Treatment with BrdU in vitro but not in vivo produces significant chromosome aberrations. About 50% of chromosome aberrations found after treatment in vitro were at the BrdU-sensitive fragile site compared with 12.5% after treatment in vivo. These results show that BrdU is much more potent in vitro than in vivo in inducing both chromosome aberrations and the expression of the BrdU-sensitive site.

Comparison of expression of the fragile site at Xq27 in T and B lymphocytes.

We compared the fragile X (fraX) expression in T and B lymphocytes from four hemizygous males with fraX. Blood cultures were stimulated with a T cell mitogen (phytohemagglutinin:PHA) and with a B cell mitogen (pokeweed mitogen:PWM). A significant decrease in fraX expression was observed in cultures stimulated with PWM when compared to PHA-stimulated ones.