[The diagnosis of idiopathic epilepsy in children based on the algorithm of molecular-genetic studies]. / Diagnostika idiopaticheskikh form epilepsii u detei na osnovanii algoritma molekulyarno-geneticheskogo issledovaniya.

AIM: To study mutations and polymorphisms in the sodium channels genes, determining the development of idiopathic epilepsy (IE). MATERIAL AND METHODS: The study of SCN1A gene by direct Sanger sequencing in 53 patients and targeted resequencing of the regions of 34 genes in 40 patients with different clinical forms of IE was performed. RESULTS: Seven mutations (c.3022G>T, c.3637C>T, c.1144G>T, c.80G>C, c.1603C>T, c.2427G>A and c.1131A>C) were detected among 53 patients by direct Sanger sequencing of SCN1A gene. The mutations of SCN1A gene (2 - nonsense mutation, 5 - missense mutation) were identified in 7/40 (17.5%) patients with epilepsy using high-performance sequencing, Mutations in sodium channel genes encoding other subunits: SCN1B, SCN2A, SCN9A were identified in 6 patients. CONCLUSION: As epileptic encephalopathy is polygenic, it is important to conduct genetic testing of more genes (primarily sodium channel genes - SCN1B, SCN2A, SCN9A etc.) using special gene panels to find the molecular defect in DNA.

[The frequency of chromosome aberrations in the lymphocytes of children with thyroid diseases living in Bryansk Province]. / Chastota aberratsii khromosom v limfotsitakh detei s zabolevaniiami shchitovidnoi zhelezy, prozhivaiushchikh v Brianskoi oblasti.

The number of unstable chromosome aberrations was determined in peripheral blood lymphocytes from 15 children with thyreopathology living in Klintsy (Bryansk Province); the mean age was 14 years. The number of dicentric chromosome is determined to be (0.18 +/- 0.07) per 100 cells and is significantly higher than that in cells from healthy children of Klintsy and Moscow (control). There was no differences in the frequency of other types of chromosome aberrations as well as of aberrant cells.

[The cytogenetic examination of different groups of children living in regions of Bryansk Province contaminated as a result of the Chernobyl accident]. / Tsitogeneticheskoe obsledovanie razlichnykh grupp detei, prozhivaiushchikh v raionakh Brianskoi oblasti, zagriaznennykh v rezul'tate Chernobyl'skoi avarii.

The frequency of chromosome aberrations (CA) was studied in peripheral blood lymphocytes from healthy children and children with thyreopathology living in the city of Klintsy, Bryansk Province (contamination level up to 5 Ci/km2), and two Moscow groups, respectively. We have observed the elevated number of dicentrics and acentric fragments in cell from children with thyreopathology with respect to those from healthy children living in Klintsy. This fact cannot be explained by influence of disease because there was no difference in cytogenetical markers between the groups of healthy children and children with thyreopathology from Moscow. The number of dicentrics was increased in cells from children with high level of internal contamination (more than 400 nCi) living in Krasnaya Gora (15-40 Ci/km2). It is proposed that the internal irradiation is more important for the CA induction. The symmetrical translocation analysis using the method of fluorescence in situ hybridisation (FISH) has shown the absence of this type of aberrations in cells from children with high level of internal irradiation whereas the translocations frequency in cells from control children was (1.1 +/- 0.4) per 1000 cells.

[An evaluation of the radioprotective action of antioxidants on normal human cells and in genomic diseases by using different cytogenetic tests]. / Otsenka radiozashchitnogo deistviia antioksidantov na kletki cheloveka v norme i pri bolezniakh genoma s pomoshch'iu razlichnykh tsitogeneticheskikh testov.

In studying the radioprotective action of natural and synthesised antioxydants a decreased yield of chromosome aberrations with respect to those in untreated cells was noted in normal cells irradiated in phase G1 whereas no radioprotective effect was found in cells irradiated in G0. The addition of antioxydants into the cell cultures from patients with Turner's syndrome did not change their radiosensitivity. No adaptive response was induced in lymphocytes from patients with Down's syndrome cultivated with vitamin E.

Adaptive response in irradiated human lymphocytes: radiobiological and genetical aspects.

The adaptive response (AR) in human lymphocytes in different experimental protocols was investigated. The AR was found to be present in cells pre-exposed to 3 cGy of X-rays in G0, G1 and S phase as well as with tritiated water (4 muCi/ml) when the 'challenge' dose was given in G2. There was no AR after prior exposure of the cells in S phase to secondary irradiation from 70 GeV protons. The AR was not observed after preliminary X-irradiation of the lymphocytes in G0 and G1 and 'challenge' irradiation in G1. Cells from 6 patients with Down's syndrome were tested. At least 5 of them did not show the AR. The AR is considered to be a phenomenon of the antimutagenic aftereffect.

[State of the neuroendocrine system in children with congenital defects of development dependent on changes in the karyotype]. / Sostoianie neiroéndokrinnoi sistemy u detei s vrozhdennymi porokami razvitiia v zavisimosti ot izmenenii kariotipa.

Forty children with multiple congenital developmental abnormalities (MCDA) without any visible changes in the karyotype and 36 MCDA children having visible changes in the karyotype were examined for the status of the neuroendocrine system. The children's age ranged from 10 days to 3 years. The children with MCDA manifested dysfunction of the neuroendocrine system, determined by the blood serum content of a number of hormones of the pituitary and the insular apparatus of the pancreas. The neuroendocrine dysfunction appeared to be in a reverse relationship to the intensity of the clinical signs (organic damage to the nervous system, delayed physical development, developmental abnormalities and minor developmental abnormalities). It manifested itself to the greatest degree in patients with numerical and structural chromosomal rearrangements and might be related to morphological or functional failure of the neuroendocrine system on the whole or of one of its components.

[Chromosome instability in diseases of the nervous system]. / Nestabil'nost' khromosom pri zabolevaniiakh nervnoi sistemy.

The authors review both their own findings and literature data about chromosomal instability in neurologic diseases. The genetic mechanisms responsible for the development of chromosomal instability and its role in the pathogenesis of different diseases of the nervous system are discussed.

[Radiosensitivity of chromosomes in lymphocytes from Down's syndrome patients]. / Radiochuvstvitel'nost' khromosom limfotsitov bol'nykh s sindromom Dauna.

A study was made of the yield of chromosome aberrations in gamma-irradiated G0 peripheral blood lymphocytes from 6 patients with different forms of Down's syndrome. The doses used were from 0.25 to 3.0 Gy. Seven healthy donors of different age made the control group. There was a significant increase in the yield of chromosome exchanges in lymphocytes from all the patients as compared to control. The spontaneous level of chromosome aberrations and the frequency of radiation-induced fragments did not differ from the control values. The yield of exchanges in diploid and trisomic cells from patients with the mosaic form of Down's syndrome did not change significantly as the time of cultivation was raised. The origin of DNA repair defects leading to the increased chromosome radiosensitivity in Down's syndrome is discussed.

[Rare case of mosaicism for chromosome 18, karyotype: 46, XX, del(18) (p11)/46, XX, i(18q)]. / Redkii sluchai mozaitsizm po khromosome 18, kariotip: 46, XX, del(18) (p11)/46,XX, i(18q).

Rare mosaicism of chromosome No 18 is described. The proposita is 5.5 years old and has two cell clones: 50% of cells are monosomic for 18p and 50% have isochromosome i18q. The ratio of these clones (1:1) is found to be similar at the age of the proposita 2.5 and 5.5 years. The proposita has some phenotypic characters of both 18p- (ptosis, epicanthus, deformed carious teeth, falled back sternum etc.) and trisomy 18q (contraction of external auditory meatus, femur luxatus congenitus etc.) syndromes. A possible mechanism for the origin of such a mosaicism is discussed.

[Phenotypic disorders in balanced reciprocal translocation: karyotype 46,XY,rcp(13; 21)(q22; q22)]. / Fenotipicheskie narusheniia pri sbalansirovannoi retsiproknoi translokatsii: kariotip 46,XY,rcp(13; 21)(q22; q22).

Clinical and cytogenetical analyses of a 2-month child revealed multiple congenital malformations and minor abnormalities characteristic of 13q- and 21q-syndromes. Phenotypic disturbances seem to be due to a balanced reciprocal translocation between the long arms of chromosomes 13 and 21 with breakage points in 13q22 and 21q22. A possibility of the position effect of genes located near the breakage points is discussed as a reason of the features observed.

[Mosaic variant of the translocation form of syndrome 18q-]. / Mozaichnyi variant translokatsionnoi formy sindroma 18q-.

A mosaic form of 18q-syndrome is found, apparently due to de novo translocation at the early stages of embryogenesis. About 60 per cent of cells have disbalanced chromosome set as a result of translocation between chromosomes 13 and 18 and the loss of chromosome regions 13q11 and 18q23, the rest 40 per cent of cells being normal. Clinical features of the proposita are supposed to be conditioned mainly by the loss of the chromosome protein 18q23. Deviations from a classic pattern of the syndrome may be explained by the loss of a proximal part of chromosome 13 and by the mosaic status of abnormality. The case described is considered as a unique translocation and a rare mosaic form of the 18 q-syndrome.