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Suspitsin E.N.,Saint Petersburg Pediatric Medical University | Sokolenko A.P.,Saint Petersburg Pediatric Medical University | Lyazina L.V.,Saint Petersburg Pediatric Medical University | Preobrazhenskaya E.V.,Nn Petrov Institute Of Oncology | And 2 more authors.
Molecular Syndromology | Year: 2015

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by obesity, postaxial polydactyly, retinitis pigmentosa, mental retardation, and kidney abnormalities. At least 19 genes have been shown to be associated with BBS, and therefore, genetic testing is highly complicated. We used an Illumina MiSeq platform for whole exome sequencing analysis of a family with strong clinical features of BBS. A homozygous c.1967-1968delTAinsC (p.Leu656fsX673; RefSeq NM-176824.2) mutation in BBS7 was identified in both affected children, while their healthy sibling and the non-consanguineous parents were heterozygous for this allele. Genotyping of 2,832 DNA samples obtained from Russian blood donors revealed 2 additional heterozygous subjects (0.07%) with the c.1967-1968delTAinsC mutation. These findings may facilitate the genetic diagnosis for Slavic BBS patients. © 2015 S. Karger AG, Basel.

Tiili E.M.,Finnish Institute of Occupational Health | Antikainen M.S.H.,Finnish Institute of Occupational Health | Mitiushkina N.V.,Nn Petrov Institute Of Oncology | Sukhovskaya O.A.,Institute of Pulmonology | And 2 more authors.
Pharmacogenetics and Genomics | Year: 2015

Objective Cigarette smoking is one of the most influential environmental factors affecting the DNA methylation patterns. The addiction-causing substance of tobacco smoke, nicotine, has also shown the potential to alter DNA methylation patterns. However, genetics has a strong influence on DNA methylation patterns, which in turn may affect an individual's smoking behaviour. Materials and methods We studied eight functional gene variants of one of the most important drug-metabolizing enzymes, CYP2D6, in relation to smoking behaviour in our well-characterized study population consisting of 1230 Whites of Russian origin. In addition, potential associations between methylation levels in a CpG island in the CYP2D6 gene and sex, age, different smoking-related phenotypes and CYP2D6 genotypes were studied. Results Both age and sex were found to be associated with the methylation level of the CYP2D6 gene. The CYP2D6 methylation pattern also showed high genotype dependence; compared with the extensive metabolizer genotype, the poor metabolizer genotype occurred notably more frequently with higher methylation status (odds ratio 5.05, 95% confidence interval 2.14-11.90). Moreover, higher methylation levels were found to be related inversely to heavier smoking (odds ratio 0.56, 95% confidence interval 0.35-0.91). We also found associations between the CYP2D6 genotype and smoking habits; the poor metabolizer genotype tended to decrease the risk of becoming a heavy smoker compared with the extensive metabolizers, whereas the ultrarapid metabolism-related genotypes tended to increase the risk. Conclusion The CYP2D6-related metabolic capacity seems to be related to cigarette consumption both through genetic and through epigenetic mechanisms. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Moiseyenko V.M.,City Cancer Center | Chubenko V.A.,City Cancer Center | Moiseyenko F.V.,Ii Mechnikov North Western Medical University | Zhabina A.S.,Nn Petrov Institute Of Oncology | And 5 more authors.
Medical Oncology | Year: 2014

Ovarian carcinomas (OC) arising in BRCA1 and BRCA2 mutation carriers demonstrate pronounced sensitivity to platinum-based therapy due to deficiency of double-strand break DNA repair. However, the choice of subsequent treatment lines for this category of women remains complicated. We considered mitomycin C for heavily pretreated hereditary OC patients, based on multiple evidence for BRCA-specific activity of this drug. Twelve patients carrying BRCA1 germ-line mutation were included in the study. All women had a history of surgical intervention followed by adjuvant platinum-based therapy; three patients also received platinating agents prior the operation. The number of preceding treatment lines for metastatic disease was one for three patients, two for four patients, three for two patients, four for two patients and six for one woman. Administration of mitomycin C (10 mg/m2, every 4 weeks) resulted in one complete response (duration 36 weeks), two partial responses (duration 36 and 48 weeks) and six instances of disease stabilization (duration 12, 16, 20, 24, 24 and 24 weeks). In addition, three patients with the stable disease showed a decline of CA-125 level. We conclude that mitomycin C may deserve further evaluation in clinical trials involving BRCA1/2-related cancers. © 2014, Springer Science+Business Media New York.

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