PROGNOSTIC VALUE OF MOLECULAR GENETIC AND BIOCHEMICAL MARKERS IN THE DIAGNOSIS OF CONGENITAL PATHOLOGY
Authors: T. V. Zhukova , A. V. Beleckij , L. M. Shevchuk , D. K. Tesakov , A. V. Borisov , K. A. Samochernyh , N. E. Ivanova , Yu. M. Zabrodskaya 
Published: February 2025

Etiological factors in the development of congenital deformities of the spine, as well as any congenital pathology, may be the effects of adverse factors and teratogens during embryonic development (valproic acid, alcohol, hyperthermia, insulin-dependent diabetes in the mother, etc.). There are also hereditary forms due to the presence of mutations in the genes involved in the laying and development of connective tissue. Materials and methods. The studies were carried out in 52 patients with congenital spinal deformities. Polymorphisms of detoxification genes GSTT1, GSTM, GSTP1 (lle105Val), GSTP1 (Ala114Val) were studied. To study mutations in the genes responsible for the growth rate and structure of the vertebrae and intervertebral discs – the HOXA11, HOXD13, RUNX2, CHST3, DLL3, MESP2, LFNG, HES7 genes, primers were developed for amplification and sequencing of the coding exons of these genes. At the same time, the microelement composition of the blood (Zn, P, Ca, Cu), as well as the content of Se, Ag, Pb, Cd were studied in 52 patients. To measure the content of heavy metals cadmium and lead, as well as trace elements of silver in biosubstrates, an Agilent 240Z AA atomic absorption spectrometer with electrothermal atomization was used; to measure the selenium content, an atomic emission spectrometer with an Ultima-2 inductively coupled plasma was used. We also studied Zn, P, Ca, Cu «macroelements», the concentration of which in the body exceeds 0.01 %. Results and its discussion. When conducting a genetic study, two mutations were identified in the HOXA11 and LFNG genes in two different patients, which are responsible for the development of connective tissue in general. In patients, there were gene polymorphisms, as well as deletions / insertions that are not pathogenic and either do not lead to an amino acid substitution in the protein or are a normal variant found in the normal population. As a result of the analysis of the data obtained in the study of trace elements and heavy metals, it was found that the ranges of values for the content of trace elements in the blood serum of children with progressive congenital spinal deformities are, μg/l: for lead – 0.001–246.460; cadmium – 0.001–3.387; silver – 0.001–165.786; selenium – 0.001–52.26 with medians, respectively, 0.001; 0.001; 3.819 and 14.650. An analysis of the lead content in the blood serum of children with bone pathology showed that in 32.7 % of the samples the content of this element exceeded the “conditional” norm by 2 times. The content of selenium in the blood serum of children is significantly below the “conditional” norm, while even the maximum value (52.26 μg/l) does not reach the lower limit of the re- ference range, the concentration of cadmium corresponds to the norm, in 86.4 % there was an increased content of phosphorus in the blood. Serious mutations have been observed in children with combined congenital malformations. They were combined with the absence of detoxification genes against the background of an increase in the content of lead and phosphorus in the blood of the subjects.
Conclusions 1. The presence of mutations in the genes responsible for the development of connective tissue as such can lead to the presence of multiple congenital pathologies. 2. The most dangerous are the variants that correlate with an increase in the reference values of heavy metals such as lead and phosphorus in the absence of detoxification genes. 3. Conducting research using the determination of molecular genetic and biochemical markers in the diagnosis of congenital pathology is a promising direction, since it can be used to search for congenital pathology, along with radiation research methods.