Presumed homozygous Ehlers-Danlos syndrome type I in a highly inbred kindred.

While studying an extended family of individuals with the Ehlers-Danlos (ED) syndrome type I, we found an affected male who was born to 2 affected consanguineous parents. This man had a more severe condition than that of his other affected relatives. Moreover, all 6 of his children were affected. Taking the pedigree data into account, the conditional probability of homozygosity for the ED gene in that patient was calculated as 97%. Some problems of the clinical and genetic approach to the recognition of the homozygous state in the ED syndrome are discussed using this family as an example.

[Various characteristics of the structure and synthesis of procollagens produced by cultured skin fibroblasts from patients with Danlos-Ehlers syndrome type I]. / Nekotorye kharakteristiki struktury i sinteza prokollagenov, produtsiruemykh kul'turami fibroblastov kozhi bol'nykh s sintromom Elersa-Danlo I tipa.

The electrophoretic mobilities of the collagen and procollagen type I and III chains synthesized by the fibroblasts isolated from patients with type I Ehlers-Danlos syndrome as well as a set of peptides obtained by splitting of pro alpha 1(I) and pro alpha 2(I) type I procollagens by cyanbromide are not different from the normal ones. The fact demonstrates the absence of long insertions or deletions, or the sufficient defects in intracellular chain modifications. The changes were also nor registered for the ratio of type I and III collagens from the digested by pepsin preparations of protein accumulating in the culture media of the cultured skin fibroblasts from patients. The studied strains of cultured fibroblasts from patients suffering the Ehlers-Danlos syndrome have the trend to increased accumulation of partially processed chains of proc alpha 1(I) and proc alpha 2(I) type I procollagen and to the increased ratio of pro alpha 1(I) to pro alpha 2(I).

[Genetic analysis of the Ehlers-Danlos syndrome in a large family tree]. / Geneticheskii analiz sindroma Elersa-Danlosa v bol'shoi rodoslovnoi.

The results of genetic investigation of Ehlers - Danlos syndrome in the kindred of 205 members are presented. The autosomal dominant inheritance hypothesis was tested using two modes of ascertainment, complete and truncated. The data from the segregation analysis provide evidence for the Ehlers - Danlos syndrome type I being inherited as an autosomal dominant trait.

[Analysis of the patient contingent at a specialized pediatric clinic]. / Analiz kontingenta bol'nykh detskoi spetsializirovannoi kliniki.

Clinico-syndromologic, cytogenetic and biochemical screening embraced 330 patients of a specialized pediatric clinic. Of all cases of diseases 78.8% were either fully or partially accounted for by hereditary factors: 54% chromosome-related syndromes, 5.2% monogenic syndromes, 3.6% nonclassified combinations of developmental anomalies 16% isolated congenital defects of development. Others (21.2%) displayed the organic CNS defects, embryo- and fetopathies due to environmental impacts. The study resulted in diagnosis changes in 6.7% of the cases and identification of 14 hereditary syndromes. The prevalence of hereditary pathology in the morbidity structure of this contingent strongly suggests the necessity of medical genetic consultation in their families.

[Hereditary pathology of the enamel and dentin. A review of molecular genetic research]. / Nasledstvennaia patologiia émali i dentina. Obzor molekuliarno-geneticheskikh issledovanii.

Mapped phenotype of imperfect amelogenesis, type II imperfect dentinogenesis, hereditary opalescent dentin, Capdepont's dysplasia, and type II dentin dysplasia is described for the first time in Russia. Classification of hereditary disorders in dentin development is presented.

[An analysis of the interrelationship of the HLA genotype and carbohydrate metabolism in the families of probands with insulin-dependent diabetes mellitus]. / Analiz vzaimosviazi HLA-genotipa i sostoianiia uglevodnogo obmena v sem'iakh probandov s insulinzavisimym sakharnym diabetom.

A total of 15 families were investigated: probands with insulin-dependent diabetes mellitus and their relatives of the 1st degree of progeny (43 persons) in order to study the distribution of HLA antigens and their interrelationship with the gravity of a course of diabetes mellitus and the type of GTT. Antigens DR3 and/or DR4 were revealed in 93% of probands, especially in heterozygous patients (57.1%). A low level of C-peptide (0.21 +/- 0.03 ng/ml) was noted in most of the probands excluding 3 patients with nephropathy. Distinct relationship of antigens DR3 and DR4 with a clinical course of disease and its severity was undetectable. Antigens DR3 or/and DR4 were detected in 96% of the relatives with the prevalence of antigen DR4 (in 54.2%). During GTT normal tolerance was observed in 82.1% (23 persons), disorders were noted in 4, insulin-dependent diabetes mellitus--in one. Most of the relatives (82.6%) with normal glucose tolerance had antigens DR3 and/or DR4. Irrespective of the type of DR antigens the probands' relatives were characterized by moderate hyperinsulinism (by the results of IRI and C-peptide of blood serum).

Enzyme-linked immunoassay and electrophoretic separation of collagens secreted by cultured skin fibroblasts of patients with Ehlers-Danlos and Marfan syndromes.

A method for the quantitation of the collagen types I, III, IV, and V, synthesized by cultured dermal fibroblasts is described. Collagens precipitated from the culture medium and intracellular collagens were detected by enzyme-linked immunosorbent assays with rabbit polyclonal monospecific antibodies. The assay could detect 10 ng protein per well, and intraassay coefficients of variation were less than 5%. Secreted collagens types I and III were also analysed by electrophoretic separation of [3H]-labelled alpha-chains under nonreducing and reducing conditions. These methods revealed a structural abnormality in one patient with clinical features of Marfan syndrome, and led to the postulation that the abnormality resulted from substitution of cysteine for another amino acid in collagen type I. In other patients an increase in the ratio of collagen type III:type I was detected, which may be secondary to an unknown biochemical defect.