The genetic polymorphism of glutathione- S-transferase M1 (GSTM1) and glutathione- S-transferase T1 (GSTT1) genes and the cytochrome P4501A1 gene responsible for xenobiotic conjugating enzymes of the phase II and phase I detoxification system were studied by PCR-RFLP in the blood spots of 109 patients with atopic bronchial asthma and 90 healthy individuals. GSTM1 gene deletion (GSTM1(0/0)) was detected in 47.8% of individuals in the control group and in 76.1% of asthmatic patients. Individuals without the GSTM1 gene were at approximately 3.5--fold higher risk of developing asthma. The proportion of GSTT1(0/0) genotypes was significantly higher in the group of asthmatics (67.0%) than in controls (23.3%). The proportion of individuals with a deficiency in both GSTM1 and GSTT1 gene activity was more than four times higher in asthmatic patients than in the control group (54.1% and 12.2%, respectively). The frequency of the Ile-Val polymorphism of the CYP1A1 gene was similar in controls and asthmatic patients. This study shows the association of atopic bronchial asthma with GSTM1(0/0), GSTT1(0/0) genotypes.

A 13 year old girl referred for chromosome analysis because of disproportionate short stature (short neck, curved legs, pectus excavatum) with an initial clinical diagnosis of Turner's syndrome was found to have the karyotype 46,X, + der(X) in 100% of her blood lymphocytes. By means of conventional differential staining (QFH/AcD, FPG, and RBA banding) supplemented with distamycin A treatment, the karyotype of the proband was interpreted as 46,X,t(X;Y) (p22.3;ql 1). The rearranged marker X chromosome was found to be active in 91% of lymphocytes studied.

From a total of 490 cystic fibrosis (CF) high-risk families under supervision (mostly Russian Slavs from the European part of the country), DNA data including both direct screening for some CF gene (CFTR) mutations (delF508, G551D and 1677delTA) and allelic polymorphism studies with tightly CF linked DNA markers were collected from 261 families. All full families (129) and 86 CF families with a decreased index child were found to be either fully (42 per cent) or partially (40 per cent) informative for DNA analysis. Prenatal diagnosis (PD) was carried out in 161 CF families. Microvillar enzyme (MVE) assay was applied to all 140 PD at the second trimester either as a single test (88) or in conjunction with DNA analysis (52). The frequency of false-negative results of the MVE assay was 1.3 per cent and that of false-positive results, as judged by the albumin meconium test, was 5.0 per cent. Ambiguous results of MVE analysis were found in 30 cases, 12 of which were verified by DNA analysis. Molecular diagnosis of CF at the first trimester was carried out in 21 cases and four pregnancies were terminated. Altogether, 39 pregnancies with a predicted high risk of CF fetuses were terminated. The low average frequency of delF508 in CF chromosomes of Russian Slavs (50 per cent), its remarkable inter-population variation, and the significant proportion of at-risk families without an affected child determine the necessity of combined molecular and biochemical (MVE assay) approaches for efficient prenatal diagnosis of CF in the former U.S.S.R.

Single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing of exons containing ATP-binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was performed on 80 Russian DNA samples. Two new alterations--S1196X (exon 19) and W1282R (exon 20)--and two novel polymorphisms--1525-61 (intron 9) and 1716+12 T-C (intron 10)--were identified. Mutation S1196X changes a TCA codon to TGA and destroys an EcoRI site. Alteration W1282R results from a T-to-C change at position 3976. It was found in one Russian patient and creates an AciI site; however, it is unclear whether this is a disease-causing mutation or a polymorphism. Polymorphism 1525-61 results from an A-to-G change. Alteration 1716+12 T-C was found in a Moldovian patient and creates a new MaeII site. It is not known whether this alteration affects the splicing of the mRNA. The previously described A4002G polymorphism was encountered in approximately 9% of Russian CF chromosomes. In addition, we have found the previously described 3732delA mutation in 7 CF chromosomes, making it the second (after delta F508) most frequent mutation in the Russian population.

No abstract