Two brothers with presumed Baller‐Gerold syndrome, one of whom was previously diagnosed with the association of vertebral, cardiac, renal, limb anomalies, anal atresia, tracheo‐esophageal fistula (VACTERL) association with hydrocephalus, were evaluated for chromosome breakage because of severe thrombo cytopenia in one of them. Spontaneous and clastogen‐induced breakage was markedly increased in both patients as compared to control individuals. Clinical manifestations and chromosome breakage, consistent with Fanconi anemia, in patients with a prior diagnosis of either Baller‐Gerold syndrome, reported earlier in one other patient [Farrell et al., 1994: Am J Med Genet 50:98–99], or with VACTERL association with hydrocephalus, recently reported in 3 patients [Toriello et al., 1991: Proc Greenwood Genet Center 11:142; Porteus et al., 1992: Am J Med Genet 43:1032–1034], underline the clinical heterogeneity of Fanconi anemia and raise the question of whether these syndromes are distinct disorders or phenotypic variations of the same disease. © 1995 Wiley‐Liss, Inc.

Genome exposure studies were carried out on malignant CHO-K1 and C6 rat glioma cells and their respective, phenotypically normal counterparts (reverse-transformed CHO-K1, and both reverse-transformed C6 glioma and normal rat fibroblasts). Cells were subjected to the nick-translation technique previously developed to make visible the exposed (i.e., DNase I-sensitive) nuclear DNA, and examined by both epifluorescence and confocal microscopy. The confocal microscopy, by permitting examination of sections throughout the nucleus, made possible clearer identification of the regions of exposed and sequestered DNA in the cells studied. A peripheral shell of exposed DNA with some discontinuities was displayed in the great majority of the cells with normal phenotype, but in none of the cancer cells. Both types of cells displayed regions of exposed DNA in the nuclear interior, particularly surrounding the nucleoli. In accordance with previous theoretical proposals we postulate: the peripheral nuclear shell of exposed DNA contains differentiation-specific genes that include the specific growth-control genes and that are functional in normal cells but not in cancer; the exposed genes surrounding the nucleoli may represent housekeeping genes active in both normal and cancer cells; and the DNase I-resistant DNA in the interior of the nucleus we postulate to consist for the most part of genes specific to alternative differentiation states and to be sequestered and inactive. Previous differences in evaluation of roles of peripheral and internal DNA sensitivity to DNAse I hydrolysis appear to be reconciled by this formulation. Identification of exposed DNA may be useful in cancer diagnosis.

Objective-To assess factors influencing uptake of amniocentesis after a positive Down's syndrome screening result. Methods-Interviews of 53 Montana women with screening risks >1 in 300 after delivery. Results-Thirty had accepted amniocentesis ("yes" group) and 23 had declined ("no" group) (57% uptake). Age at delivery was significantly higher (p=0.02) for the "no" than the "yes" group (mean 35.3 v 31.7 years). The mean risk of Down's syndrome ascertained by screening was 1 in 190 for the "no" group and 1 in 115 for the "yes" group (p=0.05). Statistically significant diVerences (p<0.05) between opinions in the two groups included: (a) desire to know if the fetus had Down's syndrome; (b) perception of the burden of care for an aVected child; (c) support of doctor, spouse, and relatives for choice about amniocentesis; (d) attitudes toward abortion; (e) importance of religion; and (f) concerns about the amniocentesis procedure. The most important factor for those choosing amniocentesis was knowing if the fetus had Down's syndrome, and for those not choosing amniocentesis, attitude about abortion. Conclusion-Our results show the need for prescreening education to enable pregnant women to make informed decisions about screening for Down's syndrome and diagnostic testing. (J Med Screen 1998;5:178-182)

Reexpression of growth control and differentiation in response to physiological inducers can be demonstrated in some malignant cell lines, showing that they are not irreversibly transformed. This switch in phenotype is likely to reflect a changing pattern of gene expression, but it has not been known whether such cellular transitions involve major or only minor modulation of chromatin structure. We have studied growth control and accessibility of chromatin to DNase I in C6 glioma cells subjected to different growth regimens using an in situ nick translation assay to label the most exposed regions of nuclear chromatin. In fibroblasts and primary glia, exposed chromatin was localized mainly at the nuclear lamina. This readily labeled DNA structure was largely lacking in the malignant C6 glioma. When C6 cells were treated with dibutyryl cyclic AMP, exposed chromatin was reestablished around the nuclear periphery. This restoration of a normal genome exposure pattern required cytoskeletal integrity. Thus large-scale nuclear reorganization events proceed in parallel with phenotypic normalization. The changes in cell morphology, growth control, cytoskeletal organization, and chromatin exposure and localization are similar to the reverse transformation reaction in CHO-K1 cells, which is also regulated by the cyclic nucleotide system. Hydrocortisone and dexamethasone also restored genome exposure in C6 but less markedly than cAMP derivatives. Diverse transformed cells can thus respond to growth control stimuli with similar nuclear restructuring events, which presumably underlie changes in gene expression. Reverse transformation and redifferentiation appear to be alternative terms describing essentially the same biological phenomenon.