[Multiple endocrine neoplasia type 1 variants and phenocopies].

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease due to a mutation in the MENI tumor suppressor gene. The risk of the disease in first-degree relatives of MEN1 mutation carriers is 50%. MENI gene mutations are not identified in 10-30% of familiar MEN1 patients and in 60-80% of sporadic MEN1 cases, which can be explained by mutations in the noncoding regions of the MEN1 gene, large gene deletions or mutations in other yet unknown genes. Molecular genetic testing can exclude the diagnosis of MEN1 in patients who do not harbor the MEN1 mutation, thus revealing a MEN1 phenocopy. This obviates the need for annual screening for the early detection of other remaining components of the disease and its risk in progeny.

[Functional characterization of two novel splicing mutations in glucokinase gene in monogenic diabetes MODY2].

Two novel mutations in glucokinase (GCK) gene-G to C substitution at -1 position of intron 7 acceptor splice site (c. 864-1G>C) and synonymous substitution c. 666C>G (GTC>GTG, p.V222V) in exon 6--were identified in patients with monogenic diabetes MODY2 (Maturity Onset Diabetes of Young). GCK minigenes with these mutations were constructed. Analysis of splicing products upon transfection of minigenes into human embryonic cell line HEK293 has shown that each of these nucleotide substitutions impair normal splicing. Mutation c.864-1G>C blocks the usage of normal acceptor site which activates cryptic acceptor splice sites within intron 7 and generates aberrant RNAs containing the portions ofintron 7. Synonymous substitution c.666C>G creates novel donor splice site in exon 6 that leads to formation of defective GCK mRNA with deletion of 16 nucleotides of exon 6. Analysis of in vitro splicing of minigenes confirms the inactivating action of novel mutations on glucokinase expression.

[Personalized medicine: state-of-the-art and prospects].

A review describes general trends and directions of personalized medicine. These include, but not limited to, prediction of disease based on genomic data, diagnostics and therapy monitoring using genomic and postgenomic technologies as well as therapeutic drug monitoring and regenerative cell technologies. The personalized medicine is considered in terms of results of the Human Genome Project and succeeding Human Proteome Project. An importance of personalized approach for modern medicine is emphasized.

[Parameters of thyroid status in children and adolescents living in one of the Kaluga regions contaminated with radionuclides]. / Nekotorye pokazateli, kharakterizuiushchie sostoianie shchitovidnoi zhelezy u detei i podrostkov, prozhivaiushchikh v odnom iz zagriaznennykh radionuklidami raionov Kaluzhskoi oblasti.

Thyroid status was examined in 1214 children living in the Ulyanov district of the Kaluga region contaminated with radionuclides. Thyroid size and structure were assessed using ultrasonic examination, its function was characterized based on thyrotropin and free thyroxin measurements. Specific autoimmunity was evaluated from assays of antibodies to microsomal antigen and thyroglobulin. The resultant values were assessed with due consideration for the individual dose of 131I absorbed by the thyroid. Thyroid enlargement was detected in 21.2%, nodular goiter in 0.79% of the examinees. A reliable positive correlation was found between the degree of thyroid enlargement and 131I absorbed dose. Functional parameters (thyrotropin and free thyroxin) were within the normal range, no correlation was detected between hormonal parameters, thyroid size, and 131I absorbed dose. Antibodies to microsomal antigen were detected in 4.3%, to thyroglobulin in 7.2%, to both in 2.8% of the examinees, this being within the normal range in the population; but a relationship was detected between antibody production and absorbed dose of 131I. Hence, though no noticeable changes in the thyroid status were detected 5 years after the accident in the population examined, the revealed correlations between thyroid enlargement, presence of antithyroid antibodies, and 131I dose may be indicative of a possible growth of thyroid morbidity.

[State of the renin-angiotensin system in children with different clinical variants of congenital adrenal cortex hyperplasia caused by 21-hydroxylase deficiency]. / Sostoianie renin-angiotenzinovoi sistemy u detei s razlichnymi klinicheskimi variantami vrozhdennoi giperplazii kory nadpochechnikov, obuslovennoi defitsitom 21-gidroksilazy.

A study was made of plasma renin activity (PRA) and serum aldosterone (A) in 52 children with congenital hyperplasia of the adrenal cortex due to 21-hydroxylase deficiency. There were 40 girls and 12 boys aged 1.5 months to 14 years. Of these, 35 had the salt-losing form (group 1), 12 were with a simple virile form (group 2), and 2 with the typical disease form (group 3). By the moment of the first examination the majority of the group 1 patients had received glucocorticoids (GC) combined with mineralocorticoids (MC), group 2 had been given GC alone, and the group 3 children had been untreated. Initially PRA in both the first and second groups was higher than in the controls. However, in group 2 that difference was insignificant. The concentration of A in group 2 noticeably exceeded that in the controls and group 1. In group 3, PRA and A did not differ from normal. After the treatment was potentiated by MC (including MC administration to the group 2 patients) there was a decline of PRA and of the A level. The changes in PRA and A did not often manifest clinically and were not associated with electrolyte disturbances. In the authors' opinion, to choose adequate doses of MC, it is necessary to examine PRA and blood A level.

[Renin-angiotensin and hypophyseo-adrenal systems in children suffering from congenital adrenocortical hyperplasia resulting from 21-hydroxylase deficiency]. / Renin-angiotenzinovaia i gipofizarno-nadpochechnikovaia sistemy u detei, stradaiushchikh vrozhdennoi giperplaziei kory nadpochechnikov vsledstvie defitsita 21-gidroksilazy.

A study was made of the activity of plasma renin (APR), and the blood levels of ACTH, 17-hydroxyprogesterone (17-OHP) and aldosterone (A) in 50 children suffering from congenital adrenocortical hyperplasia as a result of 21-hydroxylase deficiency; 38 girls and 12 boys aged 1.5 mos. to 14 years were divided into 2 groups: (1) 35 with a salt losing type of disease; (2) 15 with a common virile type of disease. ARP in the 1st group did not exceed the control values and was unaccompanied by adequate secretion of A. Moderate ARP in parallel with a high level of A was noted in the 2nd group. Mineral corticoid therapy resulted in reduced ARP and A concentration, and a tendency to a decrease in the levels of ACTH and 17-OHP was noted. Variations in ARP and in the level of A did not manifest themselves clinically and were unaccompanied by electrolytic disorders. In the authors' opinion, a choice of adequate therapy for both types of disease must be based on the results of investigation of the above hormonal parameters.