[Allelic polymorphism of short tandemly repeating sequences of the HUMF13A01 and HUMCD4 loci in Russian populations from Moscow and Tomsk]. / Allel'nyi polimorfizm korotkikh tandemno povtoriaiushchikhsia posledovatel'nostei lokusov HUMF13A01 i HUMCD4v Russkikh populiatsiiakh Moskvy i Tomska.

In samples from populations of the cities of Moscow and Tomsk, analysis of allelic polymorphism of microsatellite loci HUMF13A01 and HUMCD4 was performed by polymerase chain reaction (PCR). Eight HUMCD4 alleles (115-165 bp) and nine alleles (180-230 bp) of locus HUMF13A01 were identified. In both populations, the distributions of allelic frequencies for these loci did not differ significantly. The distribution of observed genotype frequencies fitted Hardy-Weinberg equilibrium in both populations. Mendelian inheritance of these tandem repeats was demonstrated by analysis of two large families. Parameters of polymorphism information content (PIC) for the loci studied were detected; comparative analysis of allelic frequencies with similar data on several populations was performed. These short tandem repeats (STR) were proposed for use in personal identification and paternity tests.

[Deletion analysis of the dystrophin gene in patients with Duchenne's muscular dystrophy in Tajikistan]. / Analiz deletsii gena distrofina u bol'nykh s miodistrofiei Diushenna v Tadzhikistane.

The deletion spectrum of the dystrophin gene was studied in 25 patients with Duchenne's muscular dystrophy (DMD) from 23 families in Tajikistan. To detect deletions, 17 various regions of the dystrophin gene were amplified by means of polymerase chain reaction (PCR). Deletions were revealed in 13 patients from 12 families (52%). The deletion frequency differed in different gene exons, but deletions in the distal part of the gene prevailed (in 91% of cases). Deletions from exons 47 and 48 were detected in 22% of patients; deletions from exon 50 were detected in 35% of patients (73% of patients with deletions). This showed the significance of analyzing the distal part of the gene for DMD diagnostics in Tajikistan. Studying the location of deletion breakpoints revealed a "hot spot" within the dystrophin gene: right (distal) deletion breakpoints occurred between exons 50 and 52 in 73% of deletions.

Diagnosis and prevention of lysosomal storage diseases in Russia.

A special programme for the diagnosis and prevention of lysosomal storage diseases (LSD) was developed in the former USSR. All the patients from 814 families at risk were investigated using biochemical techniques. In total, 363 patients with mucopolysaccharidoses (MPS), mucolipidoses, glycoproteinoses, sphingolipidoses and other LSD were diagnosed; 55 families at risk sought prenatal diagnosis and 67 fetuses were investigated for MPS (types I, II, IIIA and IIIB, VI), Tay-Sachs disease, Sandhoff disease, GM1-gangliosidosis, metachromatic leukodystrophy, mannosidosis, Gaucher disease and multiple sulphatidosis; 17 affected fetuses were diagnosed and aborted. There was an ethnic distribution of different lysosomal storage diseases in the former USSR.

[A program of prevention of hereditary lysosomal diseases in the USSR]. / Programma profilaktiki nasledstvennykh lizosomnykh boleznei v SSSR.

The organization of genetic counselling for the families of patients with lysosomal storage diseases (LSD) was based on the interaction of the genetic counselling units of this country with a laboratory of inherited metabolic diseases of the National Research Center of Medical Genetics, USSR AMS. All the patients from 705 families at risk were examined using biochemical techniques and methods of somatic cell genetics. In total the loci differentiation was performed for 309 patients with mucopolysaccharidoses, glycoproteinoses, mucolipidoses, sphingolipidoses and other LSD. 53 families at risk (of 277) were prenatally diagnosed. 66 fetuses were diagnosed for mucopolysaccharidoses, type I, II, III, A and B, VI, Tay-Sachs disease, Sandhoff's disease, GM1-gangliosidosis, metachromatic leukodystrophy, mannosidosis, and multiple sulfatidosis. In total 18 affected fetuses were diagnosed and aborted. All the prenatal diagnoses were verified. The prevalence of mucopolysaccharidoses in two Central Asian republics was evaluated as 1:15,000. An Uneven ethnic distribution of different mucopolysaccharides in the USSR has also been shown.

[Fluorometric titration in a method of metabolic cooperation in the differential diagnosis of mucopolysaccharidoses]. / Ispol'zovanie fliuorometricheskogo titrovaniia v metode metabolicheskoi kooperatsii dlia differentsiatsii mukopolisakharidozov

Content of intracellular glycosaminoglycans (GAG) was studied in a procedure of metabolic cooperation by means of the polysaccharides fluorimetric titration in order to differentiate between various types of mucopolysaccharidoses and to establish prenatal diagnosis of these diseases. The procedure involved electrostatic interaction of fluorochrome 4,6-diamidino-2-phenylindol. HCl with GAG's. As compared with the standard radiometric method of metabolic cooperation the procedure developed exhibited higher sensitivity, which is especially important for differentiation of the mucopolysaccharidoses III (A, B, C, D) and for prenatal diagnosis of these diseases.

[Interaction of glycosaminoglycans with positively charged fluorochromes]. / Vzaimodeistvie glikozaminoglikanov s polozhitel'no zariazhennymi fliuorokrasiteliami.

Interaction of glycosaminoglycans (GAG) with cationic fluorochromes, which are used for binding with DNA, was studied in biological material (urine, extract from hyalin cartilage) obtained from patients with hereditary mucopolysaccharidoses and from healthy persons. Among the four fluorochromes studied in the reactions with standard GAG's, DAPI proved to be the most suitable fluorochrome. Quantitative fluorimetric technique enabled to estimate the GAG concentration and to evaluate the individual content of heparan-SO4 and keratan-SO4 in biological sources. Interaction of DAPI with GAG was electrostatic and depended on stereometry of DAPI-binding sites on the GAG molecule.

[Locus differentiation of hereditary mucopolysaccharidoses]. / Lokusnaia differentsiatsiia nasledstvennykh mukopolisakharidozov.

Locus differentiation of hereditary mucopolysaccharidoses (MPS) was carried out using the methods of enzymodiagnosis and metabolic cooperation. MPS loci were differentiated in 66 patients from 58 families, examined in the Centre of Medical Genetics, as well as in 21 patient from 12 families, found in Uzbek and Turkmen populations. The following MPS types were detected: MPS I H, MPS I H/Sh, MPS II, MPS III A and B, MPSIV A and B, MPS VI. Among the patients examined MPC II was the most widespread type of the disease. Ethnic dissimilarity was noted in the MPS distribution over the USSR regions.

[Characteristics of intracellular and excretory glycosaminoglycans in hereditary mucopolysaccharidoses]. / Kharakteristika vnutrikletochnykh i ékskretiruemykh glikozaminoglikanov pri nasledstvennykh mukopolisakharidozakh.

A system for detection and diagnostication of mucopolysaccharidoses (MPS) was organized to ensure the medico-genetic service of the families, where these diseases occurred. Content of intracellular and urinary glycosaminoglycans (GAG) was studied by means of a number of methods in various types of MPS. Amount of excreted GAG's was expressed as relative units to reduce the age differences. In all the patients with MPS hyperexcretion of GAG's was found, except of some cases of MPS IV, as well as the spectrum of non-dialyzed and cetyl pyridinium chloride precipitated GAG's was altered, where the latter fraction was increased and high molecular GAG's were also prevailed as compared with normal state. All the patients were divided into four classes depending on the spectrum of GAG's excreted as shown by means of electrophoresis. The data obtained in estimation of GAG's using electrophoretic technique corresponded to the results of column chromatographic analyses but the electrophoretic procedure was distinctly less labour-consuming.

[Problems in the diagnosis of hereditary metabolic defects in pediatric neurology]. / Problemy diagnostiki nasledstvennykh defektov obmena veshchestv v detskoi nevrologii.

The authors have elaborated a program of selective screening of hereditary metabolic defects (HMD) ensuring the identification of over 100 disease entities as well as a program of the biochemical diagnosis and prophylaxis of mucopolysaccharidoses. More than 3000 patients who applied for help to the medical-genetic consultative centre were examined. Data on the incidence and genogeography of HMD were obtained.