Biomedical subjects
Publications and source records attributed to D Toncheva.
A new case of a male infant with ring chromosome 14 is reported. The G banding characteristics of early metaphase chromosomes did not reveal visible deletions in the long and short arms. The present report discusses the basic symptoms characteristic of the ring 14 chromosome and also points to a certain clinical polymorphism.
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69 out of 2,304 Vietnamese males were found to be hemizygous carriers of the Gd- gene. The glucose-6-phosphate dehydrogenase (G6PD) deficiency had a polymorphic frequency in the Vietnamese population (0.0299). Genetic heterogeneity in G6PD was found - 3 G6PD variants were found among 13 G6PD-deficient males studied (G6PD Canton, G6PD Hanoi and G6PD Vin Fu). Two new variants were identified - G6PD Hanoi and G6PD Vin Fu.
High resolution analysis of the early metaphase and prometaphase chromosomes of the father of a child with malformations and mental retardation revealed inv dupl l(q21.4----q12). Almost the same was the aberration in the propositus but with a deletion of the band lq11.2 : 46,XX, inv dupl l(q21.4----q12)del lq11.2. This suggested that the malformations and mental retardation in the child were probably due to the microchromosome anomaly in the euchromatin, connected with the heterochromatin block in the father.
Cytogenetic study of a child with the presumed clinical diagnosis of retinoblastoma of the right eye revealed del. 13q12.1. Histological examination of the removed eye showed changes which were characteristic of Coats disease. This finding is discussed.
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The incidence of spontaneous abortions in women with glucose-6-phosphate dehydrogenase (G6PD) deficiency was studied. In 78 families where the wife was a heterozygous carrier of G6PD deficiency the percentage of unsuccessful pregnancies with spontaneous abortions occurring in the first trimester was higher (21.7%, calculated from 258 pregnancies) than in the control group (9.3%, calculated from 678 pregnancies.
Marker third choromosome was established in 15 patients with Balkan entemic nephropathy (BEN) by high resolutive analysis, the chromosome characterized by altered rate of band differentiation in the distal half of the long arm--shortening of the band 3q25 and faster fusion of the subbands 3q26.1 and 3q26.3, not corresponding to the stage of chromosomal contraction. The reason for the asynchronization in the band characteristic observed is admitted to be the microstructural chromosomal reconstruction--del 3q24.2.
Twenty clinically healthy relatives were studied of patients with Balkan endemic nephropathy via high resolutive chromosome analysis. Dynamic deviations in G-band structure of third chromosome was established in 10 of the subjects studied, namely--shortening of the band 3q25 and a faster fusion of subbands 3q26.1 and 3q26.3, not corresponding to the stage of chromosomal contraction. A complete coincidence was obtained between the carriership if marker chromosome A3 and the data from the biopsy studies, revealing initial morphological changes in the kidney, characteristic for Balkan endemic nephropathy.
Considerable genetic heterogeneity in G6PD was found in the Bulgarian population-14 G6PD variants isolated from 117 hemizygous carriers of G6PD deficiency. Of these, G6PD Mediterranean type was a polymorphic variant and G6PD Corinth occurred with high frequency. Two new variants were identified-G6PD Rudosem and G6PD Nedelino. In a selected group of 78 subjects with clinical manifestations, four variants were established: G6PD Mediterranian, G6PD Corinth, G6PD Seattle and G6PD Ohut II.
The incidence of carriers of the Gd(-) gene and the Rh(+) and Rh(-) alleles was studied in 10 342 Bulgarian individuals living in 306 villages in 5 districts at different altitudes above the sea level. The results showed that the presence of the Gd(-) gene is considerably less frequent in Rh(-) than in Rh(+) individuals. In populations with a high frequency of G6PD deficiency the frequency of the Rh(-) allele is low.
The isoenzyme polymorphism and kinetics of glucose-6-phosphate dehydrogenase (G6PD) in embryonal and mature brain were studied. Two types of electropherograms were found in embryonal brains: type I is characterized by two G6PD fractions: slow and fast, and in the type II a single, fast-moving G6PD fraction was seen in a single embryo. The additional studies carried out, namely reelectrophoresis following 2-mercaptoethanol and NADP treatment and the specific enzyme kinetics, i.e. altered Michaelis constant and enhanced utilization of the desamino-NADP analogue which are typical of the fast-moving fraction in embryonal brain, speak unequivocally in favor of the presence of a new, unknown, phase-specific isoenzyme of G6PD. Its synthesis takes place only during embryonal brain development. A probable autosomal localization for the gene of brain G6PD is suggested.
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Ten variants of erythrocyte glucose-6-phosphate dehydrogenase were identified in 22 patients with G6PD deficiency from three districts of Bulgaria. Corinth-like and Fayoum-like variants were the most frequent; Mediterranean, Ohut II, Kilgore, Boston, Poznan, and Panay variants and two new variants, Petrich and Gotze Delchev, were each found in one or two carriers. No correlation was revealed between clinical and biochemical polymorphism.
Genetic markers have recently been found to be much more polymorphic than expected. Such extensive human polymorphisms may be partly explained by a number of genetic and environmental factors, including infectious diseases. Malaria, which was very widespread in the past and still poses a problem in many countries today, is a good candidate for research. The association between malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency is well-known, but more should be done to determine the mechanisms responsible for this positive correlation and to confirm that malaria is a strong selective factor for many other genotypes also. The present paper refers to a WHO project on genetic markers and susceptibility to infectious diseases, which is concerned mainly with G6PD deficiency and the following genetic markers: haemoglobinopathies, including the beta-thalassaemia trait and ABO, Rh, MN, Duffy, secretory types (Ss), and human leukocyte antigens (HLA). Since malaria was eradicated in Bulgaria many years ago, human populations from this country, living at different altitudes above sea-level, were used as a model for analysis of the malaria hypothesis. The data for G6PD deficiency confirm that malaria was a selective factor in lowland areas where malaria infection was more frequent in the past. It is, moreover, apparent that in addition to malaria some other factors also play a selective role.
The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) and erbB2 genes in the etiology and progression of ovarian tumors. In our study, we used the highly reliable method of fluorescent in situ hybridization, applied on tissue microarray, containing 1006 ovarian tumors from different malignancy, histologic type and grade, and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. We established copy number changes of erbB2 in 15.30% of malignant ovarian tumors-8.16% amplifications and 7.14% gains. The frequency of EGFR copy number changes was 10.67%-3.65% amplifications and 7.02% gains. EGFR gains occurred with approximately the same frequency in malignant (7.02%), low malignant potential (8.33%), and benign (7.19%) ovarian tumors. ErbB2 amplification was associated with clear cell type of ovarian cancer (P < 0.04). No amplification of EGFR and erbB2 genes was established in tumors with low malignant potency and in benign tumors. Regarding cancer phenotype, there was no statistically significant association between erbB2 copy number changes and histologic grade as well as tumor stage of ovarian cancer. EGFR gains are early events in ovarian tumorigenesis. Our results showed similar frequencies of EGFR gains in different grade tumors, while EGFR amplification increased from grades 1 to 2 to 3.
Colorectal cancer is one of the most common neoplastic diseases and one of the leading causes of cancer-related deaths. Elevated beta-catenin levels in colorectal cancer result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of the CCND1 gene. Overexpression of cyclin D1 is observed in one third of colorectal tumors. CCND1 amplification is the main cause of protein overexpression in numerous human carcinomas. In colorectal cancer, however, no CCND1 amplification has been reported so far. The aim of this study was to determine the frequency of CCND1 amplifications and gains in a large number of colorectal carcinomas, arranged in a tissue microarray, in order to assess their role in colorectal cancer development. The copy number changes, detected by fluorescence in situ hybridization, were predominantly gains (7.6%) and only rarely amplifications (2.5%). In colorectal cancer, the CCND1 copy number increase was neither associated with the tumor phenotype (stage and grade) nor with the tumor localization (colon, rectum or sigmoid colon). In conclusion, even in a small number of colorectal tumors, CCND1 gene amplification is a possible mechanism for the increase in cyclin D1 oncoprotein.