CLINICAL SIGNIFICANCE OF BRCA1 GENE SEQUENCING AND ITS PROMOTER METHYLATION TESTING IN THE SEARCH STRATEGY FOR THERAPEUTIC TARGETS IN BREAST CANCER TREATMENT.

BACKGROUND: Currently, there is a great interest in the genetic testing of BRCA1 and BRCA2 due to the fact that for patients with breast cancer (BC) with pathogenic variants of these genes, the use of the PARP inhibitors could be also provided in addition to implemented treatment protocols. The aim of this study was to characterize the molecular genetic structure of the BRCA1 gene in BC patients without progenitor germline mutations taking into account the methylation state of the promoter region. MATERIALS AND METHODS: The study involved 210 patients with newly diagnosed BC. The most common germline pathogenic variants of the BRCA1 (185delAG, 5382insC, 4153delA, T300G) and BRCA2 (6174delT) genes were identified in the peripheral blood. A subgroup of 14 patients without progenitor pathological variants of the BRCA1 and BRCA2 genes and with a family history of cancer was randomly selected. For them, BRCA1 gene sequencing by Sanger and hypermethylation of the BRCA1 gene promoter region were analyzed. RESULTS: The following frequencies of BRCA1 mutations were determined in the general group: 5382insC - 8.6%, 4153delA - 0.5%, T300G - 0.5%. The analysis of the BRCA1 gene by Sanger sequencing revealed 11 BRCA1 gene variants in 10 out of 14 BC patients. All of them, according to the currently available data, were defined as "benign" and not clinically relevant. The frequency of the detection of hypermethylation of the BRCA1 gene promoter region in the randomly selected group of patients was 14.3%. CONCLUSIONS: In BC patients, not only common mutations but also the methylation status of the BRCA1 gene promoter region in the peripheral blood should be determined. The whole-genome sequencing of the BRCA1 gene may be the last step in determining the genetic characteristics of BC patients carried out to optimize the treatment and improve survival thanks to the higher prevalence of the progenitor mutations and hypermethylation of the BRCA1 gene promoter.

Associations of variants of folate cycle genes with features of the clinical course of severe intraventricular hemorrhages in premature infants.

BACKGROUND: Summary data indicate that it has increased attention to the study of the role of the folate cycle and the genes encoding its key components in the complicated course of the neonatal period in premature infants. Therefore, the aim of our study was to investigate the relationship of folate cycle gene variants with the features of the neonatal course in premature infants with severe intraventricular hemorrhages (IVH). METHODS: The study included 24 preterm infants with with IVHs of 3d and 4th degree that received standard clinical, laboratory and instrumental examination. RESULTS: Apgar scores at 1 and 5 minutes were significantly lower in patients with AA genotype according to variant A1298C of the MTHFR gene. The concentration of total protein on 6th day after birth was negatively correlated with the A66G variant of the MTRR gene. The mean concentration of ionized calcium in the first day after birth was higher in the subgroup of patients with the AA genotype (according to variant A1298C of the MTHFR gene). In the subgroup of patients requiring mechanical ventilation, the frequency of AA genotype according to variant A2756G of the MTR gene was significantly increased. The presence of respiratory disorders and oxygen dependence was negatively correlated with variant A1298C MTHFR. The day of surfactant administration was positively correlated with variant A1298C of the MTHFR gene. CONCLUSION: The results of this study indicate that gene variants MTHFR (C677T, A1298C), MTRR (A66G), MTR (A2756G), RFC1 (G80A) may affect the neonatal course in premature infants with severe IVH.

CYP2C19*2 gene variant (G681A, rs4244285) as a prognostic marker for the clinical course of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the most common type of paraproteinemic hemoblastosis, which is characterized by an aggressive course, high mortality and a large number of complications. The G681A variant (*2, rs4244285) of the CYP2C19 gene leads to the formation of an inactive enzyme and, as a consequence, may affect the development and course of MM. The aim of this research was to analyze the effect of the G681A variant of the CYP2C19 gene on the risk of the development of MM and its course. MATERIALS AND METHODS: The study enrolled 158 patients with MM, who underwent standard clinical and laboratory studies: cytological, general clinical, biochemical, as well as molecular cytogenetic and molecular genetic. Cytogenetic analysis of chromosome abnormalities was performed using interphase fluorescence in situ hybridization. Genotyping by the G681A variant of the CYP2C19 gene was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association was found between the G681A variant of the CYP2C19 gene and the risk of developing MM. The association between the presence of the G allele and GG genotypes with significant changes in clinical and biochemical parameters (plasma cell count, α2-globulin, calcium content) in MM patients has been established. In the presence of the G allele of the CYP2C19 gene, the development of chromosomal rearrangements del(13q14.2) or del(13q34) with significantly increased levels of albumin occurs more frequently. CONCLUSIONS: The G681A variant of the CYP2C19 gene does not affect the risk of developing MM, but it is associated with significant changes in the clinical and biochemical parameters that determine the severity of the disease and its prognosis. Further research is important to develop new target strategies and maintenance therapy for carriers of different variants of the CYP2C19 gene (G681A).

ESR1 gene variants affect FSHR-depended risk of fibrocystic mastopathy in infertile women.

BACKGROUND: The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors. AIM: To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants. MATERIALS AND METHODS: The study included 87 infertile women (45 with concomitant fibrocystic mastopathy and 42 without mastopathy). RESULTS: For rs9340799 and rs2234693 variants of the ESR1 gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ2 = 6.39, p = 0.012, OR = 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ2 = 8.06, p = 0.005, OR = 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1 genotypes combinations - 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy. CONCLUSIONS: Our study did not find an association of ESR1 gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1 gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.

A variant of TP53 gene (rs 1625895, 13494g>A) is associated with neoplasm localization in patients with uterine leiomyoma.

BACKGROUND: Uterine leiomyoma (UL) is the most common benign neoplasm of the uterus. It is still unknown surely what exactly initiates transformation of the uterine myometrial cells into UL. AIM: To study the effect of the TP53 gene variants on the risk of development and clinical features of UL. MATERIALS AND METHODS: Case-control study was performed using molecular genetic analyses of variants rs1042522 (119 G>C) and rs1625895 (13494G>A) of TP53 gene in patients with UL and comparison group of healthy women. RESULTS: Investigated TP53 gene variants were not associated with the risk of UL development. The patients with the 13494GG genotype (rs1625895) had significantly more often subserous UL (р < 0.05). In patients with heterozygous variant of TP53 - 13494GA genotype (rs1625895) intramural UL was observed (р < 0.05). CONCLUSIONS: The rs1625895 (13494G>A) variant of TP53 gene was associated with UL localization. The identified dependence of the UL localization on the TP53 gene variant could be useful for personalized approach to treatment.

Prevalence of BRCA1 and BRCA2 genes promoter hypermethylation in breast cancer tissue.

BACKGROUND: Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. AIM: To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. MATERIALS AND METHODS: Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. RESULTS: Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region - in 50% of cases, and hypermethylation of the promoter region of both genes - in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. CONCLUSIONS: The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.

ESR1 GENE RELATED RISK IN THE DEVELOPMENT OF IDIOPATHIC INFERTILITY AND EARLY PREGNANCY LOSS IN MARRIED COUPLES.

The aim of the work was to assess genetic risk of reproductive disorders in married couples, conditioned by polymorphic variants A-351G and T-397C of ESR1gene. The study involved 412 persons - 206 married couples: 69 married couples with idiopathic infertility, lasting over 5 years, and 137 married couples with early reproductive losses in their past medical history. The data of population frequencies for the European population, obtained from the open database of 1000 Genomes project, were used as a comparison group. The polymorphic variants A-351G and T-397C of ESR1 gene were investigated using the method of polymerase chain reaction with subsequent analysis of the restriction fragment length polymorphisms. It was determined that the presence of genetic variant -351GG (log-additive model of inheritance) and the combination of genotypes -351GG/-397CC of ESR1 gene was associated with the increasing risk of developing male idiopathic infertility. The association of the polymorphic variant A-351G of ESR1 gene with the increasing risk of developing idiopathic infertility (log-additive model of inheritance) and early reproductive losses (over-dominant model of inheritance) was revealed in women from the examined married couples. Significant protective effects in terms of reproductive disorders in men were found for the combinations of genotypes -351AA/-397TT and -351AA/-397TC of ESR1 gene. The obtained results demonstrated new view about the ESR1 identical genetic mechanisms of developing idiopathic infertility and early pregnancy loss in couples. These determined specificities highlight the need of conducting genetic investigations of both ESR1 polymorphic variants in couples and the significance of searching for phenotypic manifestations of investigated reproductive disorders which occurred due to genetic variants.

POSITIVE EFFECT OF BETAINE-ARGININE SUPPLEMENT ON IMPROVED HYPERHOMOCYSTEINEMIA TREATMENT IN MARRIED COUPLES WITH REPRODUCTIVE DISORDERS.

Treatment of hereditary hyperhomocysteinemia and the achievement of optimal folate status is necessary for persons of reproductive age in order to increase live birth rate. Patients are usually advised to take folic acid, a key nutrient in homocysteine remethylation. The results of study showed risk factors for hyperhomocysteinemia development in investigated married couples: male gender, MTHFR, MTR1 genes variants, lower vitamin B12 blood serum and no additional intake of vitamin B12. Since MTHFR, MTR1 genes variants affect to decrease the efficiency of homocysteine metabolic transformations, to contribute also to endothelial dysfunction in one of patients group we used betargine combined with folic acids and vitamin B12 administration. Patients group with combined administration including betargine within 2 weeks, in comparison with the group without its supplement, had significantly decreased level of homocysteine in plasma, less than 12 µmol/l (81.03% and 50% of cases, respectively). Folic acid and vitamin B12 mean values in blood serum was significantly increased in patients after two week vitamins administration including betargin. Further research is needed to establish the duration of betaine-arginine intake until the target homocysteine level will be reached, as well as to estimate the durability of clinical effect achieved after consumption.

Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.

The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may lead to serious diagnostic errors.

[DIFFERENTIATION OF NORM AND PATHOLOGY DURING SELECTIVE BIOCHEMICAL SKREENING OF LYSOSOMAL STORAGE DISEASES WITH INCREASED EXCRETION OF OLIGOSACCHARIDES].

Oligosaccharides are a class of polymeric carbohydrates, which are constituents of a glycoside portion of glycoprotein and glycolipid molecules. The lysosomal hydrolase dysfunction due to lysosomal storage disorders results in partial or complete failure of degradation of some glycoproteins and glycolipids, causing the accumulation of specific undegraded substrates in the lysosomes of cells, the formation of the great number of oligosaccharide chains and their increased excretion with urine. Our work was aimed at detailed study of the specificities of interpreting the results of thin-layer chromatography (TLC) of urine oligosaccharides in healthy persons of different age groups with the purpose of further application of these data while differentiating the norm and pathology in the course of primary selective screening of lysosomal storage disorders. The results obtained demonstrated that TLC plates for the majority of healthy persons had insignificant excretion of a number of oligosaccharides (from monosaccharides to hexasaccharides) with R(lac) > 0.15, which can be characterized as physiological oligosacchariduria, conditioned by the metabolism specificities in lysosomes. Therefore while interpreting the urine samples of patients with the suspected lysosomal storage disorder it is diagnostically reasonable to examine the TLC plates for the presence of both oligosaccharide groups, absent in the samples of healthy persons, and all the fractions with R(lac) < 0.15.

Genetic polymorphisms of the renin-angiotensin system in breast cancer patients.

BACKGROUND: Breast cancer (BC) is one of the most common cancer pathologies in women. Genetic polymorphism of genes of renin-angiotensin system (RAS) is considered to be associated with cancer development, in particular, with BC. AIM: To study the influence of polymorphic variants of genes coding for RAS components, on the risk of BC development in Ukrainian women. MATERIALS AND METHODS: In the study 131 patients with histologically proven diagnosis of BC of I and II stages were enrolled. The control group was composed from 102 women without cancer. Polymorphic variants of AGT, ACE, AT2R1 genes were studied with the use of PCR and PCR-RFLP methods. RESULTS: It has been revealed that the presence of 1166АС genotype of AT2R1 gene elevates the risk of BC development nearly 2-fold. The results of analysis for common group and subgroups distributed by age are different. For women from 18 to 35 years old the significant differences were not found. For women from 36 to 54 years old an increased risk of BC development is determined by the presence of D allele of АСЕ gene. Decreased risk of BC development was associated with the presence of combined genotypes ACE II/AGT 174TT and ACE II/AGT 235МТ. In women older than 54 years an increased risk of BC development was found to be related to the presence of genotypes 235ТT of AGT gene and 1166АС of AT2R1 gene. The presence of genotype combinations AGT 235ТТ/AGT 174ТМ and AGT 235ТТ/AT2R1 1166AA in women of this age subgroup also significantly increases the risk of BC development. CONCLUSION: These polymorphic gene variants and their associations may be considered as possible prognostic markers of BC development. The results of analysis are different in total cohort and in subgroups distributed by age.

[Frequency of gene polymorphic variants (phase II) of biotransformation of GSTT1 and GSTM1 xenobiotics among long-livers (Precarpathian region)].

The molecular genetic study of genes (Phase II) of biotransformation of xenobiotics in 166 long livers and in 169 persons of the control group living in Ivano-Frankovsk region has been done. It was found that the frequency of functionally inactive allele of GSTT1 gene in all long livers (Ivano-Frankovsk region) reached to 24,70 and in control group - 20.12%. The frequency of functionally inactive allele of GSTM1 gene in all long livers (Ivano-Frankovsk region) reached to 46.99 and in control group--54.44%. The accommodations, in which persons under study lived, were divided into zones (the environmental factor was taken into account): environment level, moderate environmental pressures, ecology. Analysis of the combination of polymorphic variants of glutathione-S-transferase genes found that people who continued living in the zone of bad ecology, the combination of allelic GSTM1 "+"/GSTT1 "+" variants was significantly higher in long livers compared to the control group--54.55 and 35.09% respectively (chi2 = 4.29; OR = 2.22 (1.04-4.75)); the combination of allelic GSTM1 "-"/GSTT1 "+" variants was significantly higher in the control group, compared to long livers--21.82 and 43.86%, respectively (chi2 = 6.15; OR = 0.36 (0.16-0.82)). The significant difference between the frequencies of combinations of allelic GSTM1"+"/ GSTT1"+" GSTM1 "+"/GSTT1 "-" GSTM1 "-"/GSTT1 "+", GSTM1 "-"/GSTT1 "-" variants in long livers (Carpathian region) living in positive ecological zone and in bad ecological one--chi2 = 6.44; OR = 0.36-6058) respectively, was found.

Association of polymorphic G1934A variant (allele *4) of CYP2D6 gene with increased risk of breast cancer development in Ukrainian women.

BACKGROUND: Breast cancer (BC) is among the most common oncologic pathology in economically developed countries where it afflicts nearly 10% of women. Polymorphism of CYP 2D6 gene is shown to be associated with increased risk of development of a number of pathologies, in particular cancer. AIM: The work was directed on evaluation of the role of polymorphism G1934A (allele *4) of CYP 2D6 gene in elevated risk of BC development in Ukrainian women. MATERIALS AND METHODS: In the study there were enrolled 85 patients (group І) with histologically verified BC diagnosis of stages I and ІІ. Clinical-genealogic study has been performed by the method of patient survey and following analysis of genealogy. Earlier obtained data on the frequency of genotypes and alleles of CYP 2D6 gene in 637 Ukrainian people have been used as a control. For determination of allele variant *4 (G1934A) of CYP 2D6 gene the method of PCR-RFLP has been used. RESULTS: An increased risk of BC development in hereditary tainted patients with genotype *4*4 of CYP 2D6 gene compared to the control group has been revealed. The frequency of *1*4 (IM) genotype has been found to be increased in the group of women with a family history of cancer (41.79%). Significant difference between the frequency of *1*1 (ЕМ) and *1*4 (ІМ) genotypes in females with PR-positive and PR-negative tumors in the group of hereditary tainted patients has been registered. CONCLUSION: In conclusion, our study has revealed an increased risk of BC development in hereditary tainted patients compared to control group with genotype *4*4 (РМ).

[Cliniko-laboratory indicators of efficiency fermento-substitution therapy of Gaucher disease in Ukraine].

The analysis of efficiency of treatment of 17 patients with Gaucher disease (GD) in Ukraine who had received fermento-substitution therapy for 2 years and more was conducted on the basis of clinical and laboratory monitoring data. Regular infusions of recombinant glucocerebroside reduced signs of hepatosplenomegaly and pancytopenia, reduced a bone pain and a bone crisis at the majority of patients with GD I type that led to considerable improvement of health state and improvement of patients life quality. Efficiency of treatment depended on regularity of drug administration, dosage and severity level of the disease at the start of the therapy. Adult patients were not seen to have corrections of bones and neurologic disorders after the treatment that confirmed necessity of an early initiation of the treatment, before formation of irreversible changes in these organs and systems. Chitiotriodase activity in blood plasma is the most complex laboratory indicator which displays activity of pathological process in patients with GD, therefore it is necessary to use it for an estimation of treatment efficiency to correct a recombinant glucocerebroside dosage.

The role of genetic determinant in the development of severe perinatal asphyxia.

The frequency of GSTT1 and GSTM1 gene deletion polymorphism was determined in a case-control study of full-term Ukrainian newborns including patients with perinatal asphyxia. Multiplex polymerase chain reaction was used for genotyping 245 full-term newborns. The investigated full-term newborns with perinatal asphyxia were subdivided in the subgroups depending of severity of perinatal asphyxia and neonatal outcome. No significant differences in allele frequencies of homorygous null genotypes of GSTT1 and GSTM1 gene were detected among newborns with moderate perinatal asphyxia and healthy control. However, association with the development of severe perinatal asphyxia was detected for the deletion polymorphism in GSTT1 gene and the combination of the GSTT1 absent/GSTM1 absent in the newborns. The study shows that severe perinatal asphyxia may develop in the consequence of genetic predisposition to this condition as compare with moderate.

Breast cancer immunohistochemical features in young women with BRCA 1/2 mutations.

UNLABELLED: Breast cancer among young women is a rare pathology. In most studies published so far, this patients group is not being analyzed separately. Particularities of this pathology require an additional examination of the immunohistochemical and molecular-genetic markers of the disease for development of the effective treatment protocols. The mutations of BRCA1/2 are the important factor impacting to the disease prognosis along the age of the patient. AIM: To compare the expression of prognostically meaningful immunohistochemical markers such as estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, Ki-67, in tumor cells of the female patients with breast cancer aged less than 36 depending on the presence of absence of mutations in CRCA1/2 genes. METHODS: Two hundred forty-eight patients aged less than 36 at the time of diagnosis of breast cancer were examined clinically. Expression of ER, PR HER-2, p53, Ki-67 was determined by indirect immunohistochemical method. mutations of BRCA1 (185delAG, o5382insC) and BRCA2(6174delT) genes were screened using multiplex PCR in 99 patients. RESULTS: Mutations of BRCA1/2 genes were found in 9.1% of patients. More aggressive clinical course of the disease was seen in mutations carriers, who had 3-years survival of only 55.6%. They did not demonstrated of ER, PR, and HER-2 in 88.0% of the cases. Whereas, patients without BRCA1/2 mutations did no express ER, PR, and HER-2 in only 42.0% of cases. There were no differences between patients with and without mutations in terms of tumor size, presence of metastases in lymph nodes, p53 and Ki-67 expression. CONCLUSION: Presence of BRCA1/2 genes mutations in young women is associated with more aggressiveness of the breast cancer (their 3-years survival is 25,5% less) and absence of the ER, PR, HER-2 receptors, which is unfavorable prognostic factor in terms of hormone therapy. These data should be taken into account at chemotherapy planning, especially in patients with early stages of the disease. There were no differences between patients with and without BRCA1/2 mutations in terms of tumor size, lymph nodes involvement, tumor histology, and p53 and Ki-67 proteins expression.

[Several risk factors of breast cancer development and prognosis of its course].

The article presents some risk factors of breast cancer development and prognosis of the disease in Ukrainian patients. The frequency of 5382ins and 185delAG mutations in gene BRCA 1 and mutations of 6174delT in gene BRCA 2 was detected in the group of patients from Ukraine.

[Molecular-cytogenetic identification of partial trisomy of a short arm of chromosome 8]. / Molekuliarno-tsitogeneticheskaia identifikatsiia sluchaia chastichnoi trisomii korotkogo plecha khromosomy 8.

We present de novo diagnosed case of partial trisomy of short arm of chromosome 8 with psyhomotoric delay and microanomalies. Inverted duplication of short arm of chromosome 8 was identified using molecular-cytogenetic method. This case is compared with literature data on the same cases. The further intensive study of such cases is necessary to delineate this chromosomal syndrome

[An analysis of the mutations in the gene of the mucoviscidosis transmembrane regulator protein (MTRP) in patients with congenital bilateral aplasia of the vas deferens]. / Analiz mutatsii v gene transmembrannogo reguliatornogo belka mukovistsidoza (TRBM) u patsientov s vrozhdennoi bilateral'noi aplaziei semiavynosiashchikh protokov.

The genetic background of congenital bilateral aplasia of vas deferens (CBAVD) was studied. Eight patients from Ukraine were enrolled in our study. In each case, the clinical diagnosis of CBAVD was confirmed by testicular biopsy. None of patients had other clinical features of CF except high level of sweet Cl. Individuals underwent genetic screening for mutations in CFTR gene. Genomic DNA from six individuals was analysed for the 9 mutations and from two patients for the 20 most common CF mutations in European population. In 3 patients, the mutation identified was delF508 and in 3 patients was found to have the R117H mutation (in all cases one mutation per individual only). Our results confirmed hypothesis that isolated CBAVD is incomplete (genital) form of cystic fibrosis.

[An analysis of human marker chromosomes originating from chromosome 21 by using in situ hybridization]. / Analiz markernykh khromosom cheloveka, proiskhodiashchikh ot khromosomy 21, s pomoshch'iu metoda gibridizatsii in situ.

Four cases of patients with additional marker chromosomes are described. The clinical, cytogenetic and molecular cytogenetic methods have been used for investigation. The identification of marker chromosomes was made by using in situ hybridization and the collection of chromosome-specific DNA probes. All marker chromosomes were determined as originated from chromosome 21 with break-points in the region between 21q11 and 21q22.