Search

The article is devoted to the main events that took place as part of the International scientific-practical conference “Penitentiary security: national traditions and foreign experience”, which took place on 11–12 October, 2018 at Samara Law Institute of Federal Penal Service of Russia. Participants’ recommendations on the improvement of the criminal and penal legislation, practice of appointment and execution of criminal penalties, ensuring penitentiary security, personnel, psychological and pedagogical support of the FPS of Russia were among the considered group of problematic issues.

By far the strongest epidemiological variable associated with aneuploidy is advancing maternal age, accounting for about two-thirds of Down syndrome births. Modern molecular methods applied to fetal material obtained at prenatal diagnosis or assisted reproduction show that this variable is present throughout pregnancy. Genetic and reproductive factors account for some of the nonmaternal cases. Environmental factors are unlikely to play a large role. The genetics of aneuploidy are generally understood but the underlying cause remains elusive. Research is now focusing on the role of cohesin, shugoshin, and spindle assembly checkpoint genes in ensuring the maintenance and segregation of chromosomes during germ cell division and maturation.

The purpose of the present study was to examine screening marker levels in Down syndrome (DS) pregnancies with and without cardiac defects and in euploid pregnancies. Retrospective series in two centers with one or more markers—ultrasound nuchal translucency (NT), first trimester maternal serum pregnancy associated plasma protein (PAPP-A), free-β human chorionic gonadotrophin (free β-hCG), and second trimester serum α-fetoprotein (AFP), unconjugated estriol (uE3), hCG, and free-β hCG. Levels were expressed as multiples of the gestation-specific median (MoM). Differences were assessed by the Wilcoxon rank sum test and 95 % confidence intervals. There were 318 DS pregnancies including 53 (17 %) with cardiac defects. Median NT was higher in cardiac defects (1.82 compared with 1.62 MoM), but not statistically significant (P = 0.17). Median free β-hCG was significantly highly reduced in the first trimester (1.14 and 2.17 MoM; P < 0.005) and similarly but nonsignificantly in the second trimester (1.59 and 2.32 MoM; P = 0.14). PAPP-A was reduced and AFP increased nonsignificantly with no material differences for uE3 and hCG. The results on NT and free β-hCG were consistent with a series of 62 euploid pregnancies with cardiac defects screened in one of the centers. The distribution of some markers differs in DS pregnancies with cardiac defects. Depending on the screening protocol, this may affect the phenotype of DS births.

There is evidence that some mothers of infants with Down's syndrome have abnormal metabolism of folate and methyl, as well as mutations in folate genes, which are features that are also seen in neural-tube defects (NTD). We therefore investigated whether Down's syndrome and NTD arise more often in the same family than would be expected from the incidence of each disorder considered separately.We studied two series of families using information obtained from medical records about maternal age, pregnancy outcome, congenital malformations, and karyotype: the first, 493 families from Israel who were at high risk of NTD (445 with a history of NTD and 48 with isolated hydrocephalus); and the second, 516 families from the Ukraine at high risk of Down's syndrome.In the families at risk of NTD, there were a total of 11 pregnancies affected by Down's syndrome in 1492 at-risk pregnancies (compared with 1.87 expected on the basis of maternal age), which was a significant increase (p0.00001). In the families at risk of Down's syndrome, there were seven NTD pregnancies in 1847 at risk, compared with 1.37 expected (p0.001).In this study, we provide direct evidence of a link between Down's syndrome and NTD. Folate supplementation before conception has the potential to reduce the frequency of Down's syndrome.

A multicentre study was carried out to determine the frequency and clinical consequences of extremely high maternal serum pregnancy-associated plasma protein (PAPP)-A. There was a total of 79 pregnancies with PAPP-A exceeding 5.0 multiples of the gestation-specific median in a series of 46 776 pregnancies tested (0.2%) at the 7 collaborating centres. Five pregnancies were lost to follow-up, one miscarried and one with Noonan’s syndrome was terminated. Of the remaining 72 that ended in a live birth, one infant had gastroschisis and five pregnancies had obstetric complications: pre-eclampsia, pregnancy-induced hypertension, gestational diabetes and two with growth retardation. Among women with high PAPP-A and no complications or adverse outcomes, there was no evidence of a substantial change in the levels of other Down syndrome markers or the extent of nuchal translucency. Three analytical methods were used to assay PAPP-A and yielded different frequencies of extremely high levels (0.05%, 0.4% and 0.6%) possibly owing to cross-reaction with another substance. We conclude that women with high PAPP-A can be reassured that there is no reason to suppose that the outcome of pregnancy will differ from those with normal levels, provided other markers are normal. If, as more centres move their Down syndrome screening practice to the first trimester, additional cases emerge with Noonan’s syndrome or gastroschisis and raised PAPP-A, this advice will need to be modified. Copyright  2003 John Wiley & Sons, Ltd.

An analysis of 190 pedigrees with Trisomy 21 suggests a cytoplasmic predisposition for the inheritance of Down syndrome and an association with other aneuploidies, non-chromosomal syndromes, autoimmune, neurodegenerative and oncological diseases.The extra chromosome seems to be responsible for the increase in free-radical intensity and the decrease of SOD-1 activity with age. The disturbance of the oxidant-antioxidant system could be the direct cause of this chromosomal nondisjunction. These data as well as the predominant maternal origin of the extra chromosome and the age-dependent incidence was the basis for the mtDNA sequencing in a donor of extra chromosome 21. Three new point, non-polymorphic mutations, not described before, were found in the following genes:- ATP-ase, G8764A and ND-5 G13243A with the same amino-acid substitutions Ala/Thr and in ND-1 G3337A-Val/Met. The mtDNA mutations detected in cases of Alzheimer's disease, insulin-independent diabetes, some cancers, and in somatically healthy people of 40 years and older could explain the connection of Down syndrome with these diseases and aging. Moreover, mtDNA analysis in patients with trisomy 21 might help to elucidate the nature of free-radical damage. This phenomenon is directly related to the manifestation of the syndrome and cannot be explained solely by the secondary SOD-1 gene dosage effect.

Study of parental/meiotic origin of free trisomy 21 in nuclear families from Russia (70 cases), Ukraine (32 cases), and 22 from Germany revealed maternal nondisjunction in 77.3% (Germany), 93.8% (Ukraine), and 91.4% (Russia), paternal origin in 13.6%, 6.2%, and 8.6%, respectively. Maternal meiosis I errors were found in 84.4% (Ukraine), 77.1% (Russia), paternal origin in 3.1% (Ukraine), 2.9% (Russia). Maternal meiosis II errors occurred in 9.4% and 14.3% and paternal in 3.1% and 5.7% in Ukraine and Russia, respectively. No significant differences were found in maternal/paternal origin among Ukraine, Russia, Germany, and published data from other European regions.

Neither the pathogenesis nor the aetiology of Down's syndrome (DS) are clearly understood. Numerous studies have examined whether clinical features of DS are a consequence of specific chromosome 21 segments being triplicated. There is no evidence, however, that individual loci are responsible, or that the oxidative damage in DS could be solely explained by a gene dosage effect. Using astrocytes and neuronal cultures from DS fetuses, a recent paper shows that altered metabolism of the amyloid precursor protein and oxidative stress result from mitochondrial dysfunction.1 These findings are consistent with considerable data implicating the role of the mitochondrial genome in DS pathogenesis and aetiology.

Despite the increasing number of reports of families with hearing impairment and mitochondrial DNA (mtDNA) mutations, the frequency of these mutations as causes of non-syndromic sensorineural hearing impairment (NSSHI) remains unknown. Mutations such as A1555G, A7445G and 7472insC have been found in several unrelated families implying they are more frequent than initially thought. We describe a family with NSSHI due to the presence of the homoplasmic mtDNA A7445G mutation in the tRNASer(UCN) gene. This is the fourth such family described with this mutation, all of different genetic backgrounds. Our study also demonstrates the difficulties sometimes encountered in establishing mitochondrial inheritance of hearing impairment in some families.

A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.