Preliminary investigation of mutations in 21-hydroxylase gene in patients with congenital adrenal hyperplasia in Russia.

Mutations in 21 hydroxylase gene were investigated in 40 Russian patients with congenital adrenal hyperplasia. Quantitative amplification/restriction procedure was used for detection of mutations involving promoter region, 3 and 8 exons. For affected chromosomes alleles of tightly linked HLA A and B genes were defined, as well as 5 different alleles or allele combinations HLA DQA1 gene. The most frequent (> 20% of chromosomes) cause of salt wasting adrenal hyperplasia in Russia is a chimeric CYP21A-CYP21B gene with normal copy of a pseudogene which results from gene conversion in chromosome with B14-DQA1 0101/0102 haplotype. The second common mutation (about 10%) is a result of intragenic recombination well-known deletion of the gene linked with A3-B47-DQA1 0201/0601 haplotype. Two other mutations were linked with A3-B35-DQA1 0401/0402 and A3-B40-DQA1 0201/0601 haplotypes.

[The steroid content of the amniotic fluid in the 1st and 2nd pregnancy trimesters in 21-hydroxylase insufficiency and in fetal central nervous system defects]. / Soderzhanie steroidov v amnioticheskoi zhidkosti v I i II trimestrakh beremennosti pri nedostatochnosti 21-gidroksilazy i porokakh tsentral'noi nervnoi sistema ploda.

A total of 103 samples of amniotic fluid obtained by transabdominal amniocentesis were examined, 52 of these from women at a high risk of giving birth to children with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency and 30 ones with fetuses with different neural tube malformations. 17-Hydroxyprogesterone was found to be a reliable marker indicating the disease in fetuses from the group at risk of hereditary 21-OH deficiency. This marker can be effectively used as early as in the 1 gestation trimester. Fetal CNS defects are associated with hypofunction of the adrenal cortex in the II gestation trimester, observed in 60-63% of cases with hydrocephalus, anencephaly, or microcephaly. Since the function of fetal adrenals is of paramount importance for the development and maturation of a fetus, it should be examined in case of developmental defects of the neural tube, in order to predict the effect of prenatal treatment.

[Diagnosis of heterozygote carrier of mutant gene of 21-hydroxylase]. / Diagnostika geterozigotnogo nositelstva mutantnogo gena 21-gidroksilazy.

Heterozygotic carriers of 21-hydroxylase deficiency were detected by prolonged ACTH stimulation test. Stepwise discriminant analysis was used for data processing, which helped derive a function: D = 0.052 x X1 + 0.05 x X2 -0.018 x X3 = 0.069, where X1 is 17-hydroxylase concentration 9 h after ACTH infusion, X2 ratio of basel hydrocortisone concentrations to 17-hydroxylase, and X3 ratio of hydrocortisone concentrations to 17-hydroxylase 9 h after ACTH of infusion. Clinical efficacy of detection of heterozygotic carriers was 85%.

[Congenital dysfunction of adrenal cortex - detection of new mutant gene of 21-hydroxylase]. / Vrozhdennaia disfunktsiia kory nadpochechnikov - obnaruzhenie novoi mutatsii gena 21-gidroksilazy.

The paper presents the results of investigations of 30 Slavic families with different types of congenial adrenal hyperplasia (CAH). The classic types of CAH were established to be associated with HLA B14 in most cases. This fact proves the presence of new mutation of 21-hydroxylase (21-OH) gene. The nature of this mutation was studied by polymerase chain reactions in two points: 3rd and 8th exons. The mutation in the third exon was recorded as deletion of 8 nucleotide pairs. The 8th exon appeared to be unchanged. The mutation in the homozygotic state causes a salt-losing type of disease with marked decreases in 21-OH activity. A significant decreases of 21-OH activity were also detected in the heterozygotic carriers during ACTH stimulation. This mutation was discovered in 28% of chromosomes of patients with salt-losing type of CAH.

[Methods for obtaining fetal blood and its characterization]. / Sposoby polucheniia krovi ploda i ikh osobennosti.

Fetal blood was collected in 83 women, 71 of these before abortions and in 12 of them with diagnostic purpose. Cardiocentesis was used in 31 cases, cordocentesis in 52. Obstetrical situation was analyzed and fetal heart beat recorded during the procedure. Blood group and rhesus appurtenance were determined in blood samples, Kleinhauer-Batke test was carried out, karyotype, HLA phenotype, and DNA analyzed. A positive result was found dependent on the adequate assessment of an obstetrical situation during fetal blood collection, as well as on equipment resolution power and physicians' experience. The possibility of practical use of cordo- and cardiocentesis is discussed with due consideration for these factors.

[Features of adrenal cortex function in heterozygous carriers of 21-hydroxylase deficiency]. / Osobennosti funktsii kory nadpochechnikov u geterozigotnykh nositelei nedostatochnosti 21-gidroksilazy.

Adrenocortical function in carriers of 21-hydroxylase insufficiency and in persons without it was investigated by change in the levels of 17-hydroxyprogesterone and dehydroepiandrosterone before and against a background of prolonged ACTH stimulation. Differences in change of the basal concentrations of these hormones in both groups were absent. Change of adrenocortical function in the carriers was observed against a background of ACTH stimulation only by the blood level of 17-hydroxyprogesterone. Prolonged ACTH stimulation revealed not only quantitative but also qualitative traits of adrenocortical function in carriers of 21-hydroxylase insufficiency. An algorithm for diagnosing this insufficiency was worked out.

[The functional characteristics of the reproductive system in women who are heterozygous carriers of 21-hydroxylase deficiency]. / Osobennosti funktsii reproduktivnoi sistemy u zhenshchen--geterozigotnykh nositel'nits nedostatochnosti 21-gidroksilazy.

This paper reports the results of evaluation of reproductive histories of 52 heterozygous female carriers of 21-hydroxylase deficiency who gave birth to children with classic congenital adrenocortical hyperplasia. Functional ACTH adrenal tests of these women were compared with those in a control group of noncarriers. Test findings are discussed with respect to the pathogenesis of reproductive tract disorders in the carriers of a mutant gene.

[17-Hydroxyprogesterone levels in the amniotic fluid during the 2d trimester of pregnancy]. / Urovni 17-oksiprogesterona v amnioticheskoi zhidkosti vo II trimestre beremennosti.

The paper is concerned with some data on the content of 17-oxyprogesterone in the amniotic liquid of a normal fetus and a fetus with CNS defects during pregnancy. The appropriateness of 17-OP investigation for a diagnostic purpose after the 20th week of pregnancy is discussed.

[Chromosomal polymorphism in patients with ovarian hypofunction of central origin]. / Polimorfizm khromosom u bol'nykh s gipofunktsiei iaichnikov tsentral'nogo geneza.

Comparative data are reported on chromosome polymorphism in adolescent patients with ovarian hypofunction of central origin and healthy women. Chromosome variants with small and very small heterochromatin blocks were found to prevail in the adolescent patients. The incidence of pericentric inversions in chromosomes 1 and 9 was found to be significantly increased in the girls with ovarian hypofunction.