Chromosome testing in children with developmental delay in whom the aetiology is not evident clinically

A review was carried out to establish the value of chromosome testing in children with significant developmental delay, where the aetiology was not evident clinically. During 1990, 315 children had been assessed at a child development clinic and found to be significantly delayed in one or more areas of development; in 256, the aetiology was not evident clinically. Chromosome testing of these children revealed an abnormality in 10 (3.9%). Thirty children had dysmorphic features; six (20%) of these had an abnormal karyotype. Four (2%) of the 226 who had no dysmorphic features had a chromosome abnormality. One hundred and fifty-five children had intellectual disability; eight (5%) of these had an abnormal karyotype. Two (2%) of 101 who had a specific delay in their development had a chromosome abnormality. The advantages of chromosome testing in children with developmental delay in whom the aetiology is not evident clinically are discussed.     

Meiotic behavior of the X1X2Y1Y2 quadrivalent of the primateAlouatta caraya

A multiple sex chromosome system was found in three unrelated individuals of the primateAlouatta caraya. This mechanism is originated by a translocation between the Y chromosome and one of the autosomes (A7). Mitotic karyotypes show two small, acrocentric chromosomes (A^Y and Y^A), which are the translocation products. In metaphase I of male meiosis, there is a very long chain quadrivalent in which the order of the element is: X–Y^A–A7–A^Y. Segregation in the quadrivalent is alternate and gives balanced products. Synaptonemal complex karyotypes at pachytene show the structure of the quadrivalent made by the four axes. There is a slight difference in the relative length of A^Y and Y^A and the kinetochore of A7 aligns with that of A^Y. The synaptic pattern and changes in the quadrivalent during pachytene are described. Thin sections of the quadrivalent body show that the chromatin packing in the sex chromosome region is different from that of the autosomal region. This X1X2Y1Y2/X1X1XX2 sex chromosome system may be extended among other members of the genusAlouatta.accepted for publication by M. Schmid     

Banding resolution of human chromosomes: A method of accuracy and simplicity

Methods of estimationg chromosome band reolution have been published but their accuracy has not been established Banding resolution was determined by 4 methods which included a computerized linear correlation, the sum of bands on chromosomes 1 and 2, interpolation of the number of bands on chromosome 10, and interpolation of the number of bands on chromosomes 1p, 10 11p, 12q, and X. The sum of bands on chomosomes 1 and 2 multiplied by 6 is the most accurate and simple. The use of a simple and reliable method is important for cytogenetic laboratories to document quality assurance of routine chromosome analyses, to enhance the exchange of information between laboratories, and to establish criteria for appropriate band resolution for specific types of specimens. © 1993 Wiley-Liss, Inc.     

The rat bladder tumor model system RBT resembles phenotypically and cytogenetically human superficial transitional cell carcinoma

Summary A cohort of 300 ACI rats was kept under standard laboratory conditions. After 30 months or upon natural death, complete autopsy was performed. In the genitourinary tract four kidney and five bladder tumors were found. Two of these bladder tumors, RBT323 and RBT157, are serially transplantable. In the fifth transplant generation the RBT323 tumor becomes metastatic to the lungs in more than 90% of animals. The metastatic ability of the RBT157 tumor changes from low to intermediate (50% of the rats have lung metastases) in the fourth passage. Histologically, the initial passages of the RBT323 and 157 tumors are grade II transitional cell carcinoma (TCC). The histological pattern of the RBT157 tumor remains essentially unchanged, whereas the RBT323 tumor progresses to a grade III tumor in the third passage. Electron microscopical studies reveal oblong elliptical and round vesicles lined by an asymmetrical unit membrane in the tumor cells, which stresses the urothelial origin of the tumors. Immunohistochemically both tumors show expression of cytokeratin 5, 7, 8 and 18. The progression of the tumors to a metastatic phenotype, however, is not associated with a specific change in the morphological characteristics. Cytogenetic analysis shows that both tumors are peridiploid with few marker chromosomes. Interestingly, both of these independently arising tumors exhibit a loss of chromosome 5. Rat chromosome 5 is syntenic to the major portion of human chromosome 9 (p23-qter). Loss of chromosome 9 is a cytogenetic trait of human superficial TCC, hence the RBT mocel is also in cytogenetic respect similar to human TCC. Two independently arising rat tumor lines that initially resemble superficial TCC both phenotypically and cytogenetically are described. Upon serial transplantation both lines progressed to a more aggressive tumor, albeit to a different extent (highly vs moderately metastatic). Thus this model system may be helpful in the identification of specific markers associated with the progression of superficial bladder cancer.     

Cytogenetic and DNA-flow cytometric studies of separated blasts

With Percoll density gradients, blasts from peripheral blood and bone marrow could be separated with a significant enrichment, and very often with a high degree of purity. This allowed a study of selected cases, where the separated sample exhibited chromosome abnormalities and/or an abnormal DNA content distribution (as measured by DNA-flow cytometry). The anomalies were shown to be associated with the separated blast fraction.     

A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH)

In seven cases additional minute chromosomes studied by FISH were identified as no. 3, 11, 15, 18, 21 and X. Findings were unexpected except for partial trisomy 21 in an adolescent with minor features of Down's syndrome. Moreover, an i(18p) in a mentally retarded dysmorphic child and an idic(15) in a child with Fallot tetralogy was confirmed. In a child with r(21), a supernumerary marker was shown to be derived from no. 21, while in the mother an additional marker idic(22) was noted.     

Chromosomes in autism and related pervasive developmental disorders: a cytogenetic study

Few studies have examined the occurrence of chromosome abnormalities in a large sample of patients with autism and related pervasive developmental disorders (PDDs). In the present report, the authors examined a consecutive series of 92 children with PDDs (DSM-III-R; 75 males and 17 females). A cycogenetic examination, including growth in folate deficient medium, was performed in all cases. Three patients (3.2%) (two females and one male) showed chromosome abnormalities: deletion of the long arm of chromosome 8; tetrasomy of chromosome 15; and XYY syndrome. Only the subject who had tetrasomy I S met the criteria for autistic disorder, while the others were diagnosed as suffering from a PDD not otherwise specified (PDDNOS). Another patient showed an abnormal fragile site at Xq27 in three out of 100 cells. However, subsequent molecular studies did not confirm the presence of fragile-X syndrome. These results suggest that chromosome abnormalities are uncommon in traditional autism and may be relatively more common in people with PDDNOS.     

High alkaline phosphatase activity in isoproterenol stimulated fibroblast cultures from patients with numerically unbalanced chromosomal aberrations

Treatment of cultured fibroblasts from patients with unbalanced chromosomal aberrations with a mixture of isoproterenol, theophylline and ascorbic acid resulted after 48 hours in an at least three-fold increase of alkaline phosphatase activity on a per cell basis, whereas cells from normal healthy individuals did not show this dramatic response. Cells were studied from patients with trisomy 21 (14 cases), trisomy 18 (3 cases), trisomy 13 (1 case), pentasomy X (1 case), Turner syndrome (2 cases), and Klinefelter syndrome (1 case), and no exception was noted. The mechanism of this phenomenon is not clear, but it is speculated that increased cyclic-AMP levels caused by the action of isoproterenol on adenylcyclase may account for excessive reactions of unbalanced cells as compared to normal cells. This simple biochemical diagnostic procedure might become useful in screening programs for unbalanced chromosomal abberations.     

Increased sister chromatid exchange associated with smoking and coffee consumption

Sister chromatid exchange (SCE) is a very sensitive cytogenetic assay for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to be exposed to such agents. We have, however, relatively little knowledge about common lifestyle factors that may influence SCE and therefore complicate any study designed to examine the effects of exposure to genotoxins. In this study, we assessed the effect of cigarette smoking and coffee consumption on SCE. Smoking was associated with an increase of approximately 2 SCEs per cell and a decrease in cell proliferation. A positive linear relationship between SCE and coffee consumption was also observed. This effect was similar for smokers and nonsmokers. Additionally, the folic acid content of cell culture medium seemed to affect neither SCE nor cell proliferation.