[Clinical and Genetic Characteristics of Russian Marfan Patients].

The results of direct DNA diagnostics in nine patients with Marfan syndrome, aged from two to 52 years old, and four unhealthy relatives with the same disease from two unrelated families have been presented for the first time in Russia. Eight mutations in the gene FBN1 were revealed. One patient demonstrated a substitution with unknown clinical importance, which was previously described in the SN P database as rsl 12287730 with a frequency of incidence of 0.1%. Out of the eight mutations, two (25%) were previously described, and the other six mutations (75%) were revealed for the first time. These mutations revealed by us were of the following types: three mutations (37.5%) produced a shift in the open reading frame (two deletions and one insertion), three mutations (12.5%) involved a splicing site, and one (12.5%) nonsense mutation was also noted. Our data contradict previous reports that claimed that the majority of mutations in the FBN1 gene represented missense mutations. Such inconsistency could result from a small size of the examined sample or from substitutions that produced alteration in the splicing site (as we have demonstrated here). The distribution of the revealed mutations was uniform along the whole gene. The results of the conducted comparative analysis of genetic and phenotypic indices was in complete agreement with previously reported results. The developed direct method of DNA diagnostics was fully informative, as we managed in all nine examined patients to confirm their clinical diagnosis using a molecular and genetic approach.

[The problem of rare (orphan) diseases in the Russian Federation: Medical and normative legal aspects of its solution].

The paper gives an update on orphan (rare) hereditary and congenital diseases and their definitions and considers approaches to estimating their incidence and prevalence and the existing problems of their diagnosis and treatment in the world and our country. It lists the hereditary diseases and syndromes belonging to rare conditions. The paper presents (considers) the most relevant problems of rare diseases, which call for priority solution.

[The diagnostic of peroxisomic diseases in children].

The article presents the results of analysis of long-chained fat acids, fitanic acid and pristanic acid using gas chromatography method. The information is provided concerning the biochemical characteristics of mentioned compounds and their biologic role. The procedure of their analysis is described. The reference values of levels of main long-chained fat acids in blood plasma are presented. The dynamics of modifications of these values under various pathologies is analyzed, including the inherited peroxis diseases in children.

Influence of buffer gas and vibration temperature of carbon clusters on fullerene formation in a carbon plasma.

A new model for calculation of fullerene formation rate in carbon containing plasma is proposed. The model takes into account carbon cluster heating and cooling during transformations due to chemical bonds formation and destruction. In addition, the heating and cooling of carbon clusters by buffer gas is considered. The calculations give the qualitatively correct correlation between fullerene yields in helium and argon.

[The use of modern diagnostic and preventive technologies in children with hereditary and congenital intellectual developmental disorders].

The article is dedicated to the problems of intellectual disorders in children suffering from congenital and hereditary diseases, and reflects the issues of the medicosocial significance of neuropsychical impairment in children and the proportion of ethiological factors in the genesis of mental retardation. The authors consider modern diagnostic and preventive technologies that are used in pediatric practice in children with hereditary and congenital intellectual developmental disorders.

[Clinical and genetic characteristics of the X chromosome distal long arm microduplications encompassing the MECP2 gene].

OBJECTIVE: Microduplications of the long arm of the X chromosome including the MECP2 gene are relatively common causes of neurodevelopmental disorders in males. Authors analyzed clinical presentations of this disease in children. MATERIAL AND METHODS: Authors performed a clinical and genetic analysis of four cases using contemporary cytogenetic, molecular cytogenetic studies (FISH, array CGH) and X chromosome inactivation analysis. RESULTS AND CONCLUSION: We described somatic, neurologic and mental symptoms of the patients. The genetic imbalance impact on the patients' phenotype, necessity of comprehensive family studies for correct genetic diagnosis and effective genetic counseling in cases of microduplications of the long arm of the X chromosome including the MECP2 gene are discussed.

[Genetic aspects of vitamin D-deficient rickets: genetic markers of blood]. / K geneticheskim aspektam vitamin-D-defitsitnogo rakhita. Geneticheskie markery krovi.

Polymorphism of the AB0 blood groups, haptoglobin Hp, vitamin-D-binding protein (Gc), transferrin (Tf), alpha 1-antitrypsin (alpha 1-AT) and serum alkaline phosphatase (Pp) was studied in a group of children suffering from rickets (VDDR) and in a adequate control group of healthy individuals of the same sex-age composition. Considerable differences were revealed between the VDDR patients and healthy individuals in frequencies of the PIM1 and PIM2 factors on the alpha 1-AT system, r and p of the AB0 system as well as the Hp. Increase in a portion of one of the homozygotes for the Hp and for the alpha 1-AT system took place at the expense of other homozygote proportion (the latter being decreased). Heterozygotes frequencies remained intact in both compared groups. Atypical combination of phenotypes and gene frequencies was observed in a group of patients in the alpha 1-AT and AB0 systems as compared with usual distribution in European population. Higher frequencies of rare alleles of the loci under study were observed in the VDDR patients, which is partially reflected in increase in heterozygosity level in total within a cogort of patients analysed. Combination of the Hp 1-1 (Hp)--A(AB0)--M2M2 (alpha 1-AT) factors should be considered as unfavourable in rickets prognosis.

[Molecular-genetic characteristics of the deleted region of chromosome 8q24.1 in Langer-Giedion and tricho-rhino-phalangeal type I syndromes]. / MOlekuliarno-geneticheskaia kharakteristika oblasti deletsii khromosomy 8q24.1 pri sindromakh Langer-Gidiona i trikho-rino-falangovom I tipa.

A molecular-genetic characterization of deletions in part of chromosome 8q24.1 was performed in patients with Langer-Giedion syndrome (six patients) and triho-rhino-phalangeal syndrome type I (three patients) by means of Southern blot hybridization analysis, restriction fragment length polymorphism and single-strand conformation polymorphism, analysis. Four families with multiple exostosis chondrodysplasia (MECD) also underwent the same analysis. Results of deletion mapping allowed determination of the probable region of localization of the proposed gene of MECD at D8S67 locus. By means of a polymorphic DNA probe obtained from the locus an additional hybridization signal was revealed only in patients with MECD. Other polymorphic DNA probes and microsatellite sequences confirmed the results of deletion mapping and detected haplotypes on the chromosomes with a mutation in the proposed MECD gene.

[Automated information-diagnostic system for hereditary diseases in childhood]. / Avtomatizirovannaia informatsionno-diagnosticheskaia sistema po nasledstvennym zabolevaniiam v detskom vozraste.

This article describes computer-based information-and-diagnostic system dealing with child hereditary diseases which makes in possible to organize automated consultative service on a wide range of monogene and chromosome syndromes. The system is oriented for sorting out a narrow differential-and-diagnostic row from 1200 of genetically determined diseases at the stage of pre-laboratory child examination. The choice of diagnoses in the system is based on the analysis of the likeness of phenotypical manifestation of the syndromes described in literature with the case under analysis. The system envisages information exchange with a physician in a dialogue using the natural language. The system is based on IBM-370 computer and can be operated from remote video device in the data TV transmitting mode.

[Automated genetic register and computer support for the physician's diagnostic decisions]. / Avtomatizirovannyi geneticheskii registr i komp'iuternaia podderzhka diagnosticheskikh reshenii vracha.

Computer-based genetical register "GENREG" allows to carry out a prophylactic medical examination for families with children, having hereditary diseases, multifactorial pathology and congenital developmental defects of various nature, and also epidemiological examination. Automated consultative system for pre-laboratory diagnosis of genetically determined diseases after the phenotypical manifestations "DIAGEN" allows to identify up to 1200 nosologic units; diagnostic value (or weight) of the signs according to physician's evaluation is taken into consideration. The system sorts out a narrow differential-and-diagnostic row and information about specific laboratory and functional changes for every selected diagnosis. Efficiency of the system is over 94% (after the next laboratory findings). The results of computer diagnosis and final physician's diagnosis, and also questionnaire of a child are stored in archives (files) of the "DIAGEN" system. Both of the systems are realized on PC/AT IBM-compatible computer.

[Medical and prophylactic aids to children with hereditary diseases in Russia]. / Lechebno-profilakticheskaia pomoshch' detiam s nasledstvennymi zabolevaniiami v Rossii.

The state-of-the-art of medical and prophylactic aids to children with hereditary diseases in the Russian Federation and the main ways of its further development are analyzed.

[Epigenetic study of Rett's syndrome as an adequate model for autistic disorders].

Rett's syndrome (RTT) is a severe hereditary disorder of the nervous system. MECP2 gene mutations are considered as a primary cause of the disease. In the present study, we have found MECP2 mutations in 33 (84.6%) out of 39 RTT females. We have also studied X-inactivation patterns in 70 girls with RTT. A frequency of skewed X-inactivation was 37% (26 patients), being significantly higher (p < 0.001) than that in the controls. The investigation of inactivated X chromosome origin revealed that about 33% pairs had preferentially the inactivated maternal X chromosome. An abnormal type of chromosome X inactivation was observed in all RTT females. Thus, we conclude that skewed X-inactivation may be considered as a common feature of RTT. There is unambiguous evidence that epigenetic alterations in RTT are associated with MECP2 mutations. MeCP2 protein also appears to be involved in transcriptional regulation of chromosome X genes. RTT in females without MECP2 mutations is related to the epigenetic alterations. We suggest X chromosome inactivation study in RTT females and their mothers to be informative for investigation of genetic processes in RTT girls, even in case MECP2 mutations have not been found. RTT could be considered as an appropriate model for studying epigenetic abnormalities in relation to autistic spectrum disorders.

[Differential diagnostic value of receptors of 1,25-dihydroxyvitamin D3 (calcitriol) determination in lymphocytes of children with rickets and rickets-like diseases]. / Differentsial'no--diagnosticheskoe znachenie opredeleniia retseptorov 1,25-digidroksivitamina D3 (kal'tsitriola) v limfotsitakh u detei pri rakhite i rakhitopodobnykh zabolevaniiakh.

The authors provide the results of studying 1,25-dihydroxyvitamin D3 (calcitriol) in lymphocytes of children with rickets and rickets-like diseases. It is proposed that the character of their expression under the influence of vitamin D may be used with differential diagnostic purposes in view.

[Main trends in the control of hereditary diseases in childhood]. / Osnovnye napravleniia bor'by s nasledstvennymi zabolevaniiami v detskom vozraste.

The results of the activity of the Department for Congenital and Hereditary Diseases of the Moscow Research Institute of Pediatrics and Childhood Surgery of the Ministry of Public Health of the RSFSR point to the efficacy of the work of the Centre for Hereditary Pathology of that Institute in the field of the diagnosis, treatment and prevention of hereditary diseases of children. The prospects of further studies are outlined.

[Genotype-phenotype correlations in Rett syndrome: the study of Russian cohort of patients]. / Kliniko-geneticheskie korreliatsii pri sindrome Retta: izuchenie rossiiskoi kogorty bol'nykh.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 gene (MECP2). We carried out a mutations analysis in Russian cohort of patients with RTT. MECP2 mutations were found in 23 of 28 RTT girls and one boy (82%). Thirteen different types of mutations have been identified: 6 nonsense, 5 missense and 2 deletions in MECP2 gene. In typical RTT form, most frequent mutations were R255X (5 cases) and T158M (4 cases). A boy with classical clinical picture of RTT had R270X mutation. Skewed inactivation of chromosome x has been found in 2 of 27 RTT girls with classical RTT form and "forme fruste". The data obtained imply possible correlations between genotype and phenotype in RTT.