Biomarkers (BM) are biological molecules that can indicate the presence of a biological process linked to the clinical manifestations of disease. This review was focused on present information about biomarkers for three groups of hereditary metabolic diseases related to the disorders of the cell organelles - lysosomal storage disorders (LSD), mitochondrial and peroxisomal disorders. Enzyme replacement therapy and other treatments are being introduced for lysosomal storage diseases (LSDs). However, apart from in Gaucher disease, there are currently very few biomarkers that are available to monitor LSDs and other disorders of cell’s organelles. In conclusion we can note, that biomarkers have a clear application in routine clinical monitoring after the developing of new drugs - and at the same time may provide opportunities for a better understanding of molecular pathogenesis of inherited diseases and developing of new treatments.

Timeliness. Hereditary spastic paraplegia (HSP) - a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity of the lower limbs. The aim. Clinical and genetic study of patient with the sporadic form of spastic paraplegia. Methods. DNA sample from patient with a sporadic form of spastic paraplegia and the DNA samples from 150 healthy individuals. Mutations identifications was carried out by direct sequencing. Results. We identified previously undescribed mutation c.1114A> G (p.Arg372Gly) in the eighth exon of SPAST gene in this patient. The clinical picture of HSP in this case corresponds to the uncomplicated form of the disease. Conclusions. This data supplement information on the clinic features and genetic of hereditary spastic paraplegia, and contribute to the development of the algorithm of DNA-diagnostics of the disease, optimal for the study region.

Wilson disease (WD) is an autosomal recessive copper accumulation disorder. ATP7B gene codes a protein which transports copper. Over 800 mutations has been identified in this gene. We present a case of 22 years old woman with clinical picture of cryptogenic hepatitis, oligomenorrhea and negative results of test for 8 frequent mutations. The sequencing of gene ATP7B had performed, and two mutations were identified: known mutation c.3190G>A (p.Glu1064Lys) and novel mutation c.3655A>T (p.Ile1219Phe). Therefore, WD diagnosis was confirmed and then copper helation therapy was started with positive effect.

Introduction: Patients with chromosomal disorders are characterized by wide clinical polymorphism, which reasons are quite varied and not always clear. For geneticist it is difficult to make an accurate diagnose because of symptoms variety in a patient. Conventional cytogenetic analysis is not always effective in identifying the genetic cause of the disease. The quality and accuracy of diagnosis is significantly increased with the use of high-resolution molecular karyotyping. Aim: The work was aimed to establish the boundaries of chromosomal mutation that led to the formation of a ring chromosome 22 and to analyze genotype-phenotype correlations in a patient with developmental delay and congenital malformations. Materials and methods: Ring chromosome 22 was revealed using the conventional cytogenetic analysis. Microdeletions 22q13.32-q13.33 and 3q13.31 were detected by aCGH (860K, Agilent Technologies). Results: The patient presented the symptoms of both syndromes (microdeletion 3q13.31 and 22q13.32-q13.33 (Phelan-McDermid syndrome): delayed psychomotor development and speech, signs of autism, frontal bossing, epicanthus, ear anomalies. Clinical features specific for 3q13.31 microdeletion were presented by attention deficit hyperactivity disorder, short and smooth filter, a thin upper lip, ventriculomegaly. Clinical features specific for 22q13.32-q13.33 microdeletion were presented by aggression, tall stature, microcephaly, bulbous nose, sacral dimple, CNS malformations, seizures, sleep disorders, heart defects. Features previously not described in any patient with either 3q13.31 or 22q13.32-q13.33 microdeletion include sloping occiput, straight eyebrows, up-slanting palpebral fissure, telekanthus, wide and depressed nasal bridge, wide umbilical ring, brachydactyly of I and V fingers of hands and all toes, thickened distal phalanx of first fingers of hands and feet, flat-valgus foot. Conclusions: The analysis shows the significance of the additional high-resolution molecular karyotyping for patients with cytogenetically visualized chromosomal abnormality in the presence of atypical clinical signs for such pathology.

Timeliness. Prostate cancer (PC) is clinically and genetically heterogeneous disorder characterized by high prevalence and mortality. The aim. Germline mutations analysis in PC patients. Methods. DNA samples from blood and normal prostate tissues from 8 PC patients. Analysis of mutations was carried using whole exome sequencing. Results. In PC patients a number of pathogenic mutations in DNA repair system genes was found. Conclusions. The data supply information on molecular characterization of PC and contribute to the genetic counseling and treatment strategies of PC.

As a result of genetic and epidemiological study the load of monogenic hereditary pathology (MHP) in 5 populations (Cherkessk, Ust-Dzhegutinsky, Karachaevsky, Malokarachayevsky, Prikubansky districts) Karachay-Cherkessia Republic (KCR) was estimated. The analysis was performed for the all population and separately for the representatives of the titular nation KCR - Karachai. The number of the surveyed population was 269,355, of whom 197,597 urban (72,896 Karachai - 36.89%) and 71 558 rural (62213 Karachai - 86.94%). Differential diagnosis of MHP carried out using modern technologies (PCR-RFLP analysis, sequencing according to Sanger, MLPA, NGS, FISH, etc.). The parameters of load AD, AR and X-linked pathology varied significantly between populations and the absolute values was similar to those that have been received for the peoples of the Volga-Ural region. The highest differentiation between the load detected by all types of MHP in urban and rural populations for the entire population (1: 349 and 1: 152 respectively), and for karachai (1: 262 and 1: 154 respectively).

This article describes 4 clinical cases of glucose transporter type 1 deficiency syndrome (GLUT1, De Vivo disease) in children admitted to the neuropsychiatric department of Scientific and Practical Center of children medical care. The drug-resistant epilepsy, movement disorders, psychomotor and intellectual disabilities, decrease of glucose levels in the cerebrospinal fluid (CSF) were diagnosed in children. The different types of mutations in the SLC2A1 gene, responded for the development of GLUT1 deficiency syndrome were detected by targeted sequencing in all patients. De Vivo disease is characterized by the infantile-onset encephalopathy, symptomatic drug-resistant epilepsy, microcephaly, delayed psychomotor development with spasticity, ataxia, dysarthria and alternating hemiplegia and decrease the level of glucose in the CSF. Currently, the ketogenic diet is highly effective method of pathogenesis therapy, which can reduce the clinical manifestations: controlling the seizures, improving the movement disorder and speech.

The case of familial (1;2) reciprocal translocation is discussed in order to illustrate major principles of genetic counseling and up-to-date diagnostic approaches used for such patients.

The athors described the case of acute porphyria polyneuropathy with an effective treatment for glucose. The disease is manifest at the age of 36 years with abdominal pain, bowel clinical paresis. After 3 weeks from the onset of the disease originated tetraparesis due to peripheral nerve lesions with a primary lesion of the proximal extremities. There was a dark urine. There was a tachycardia with a heart rate of 125 1 per minute. The qualitative urine test for porphyria with Ehrlich’s reagent, which was positive. By quantifying total urinary porphyrins porphyrins were increased more than 10 times, porphobilinogen was increased more than 100 times, delta-aminolevulinic acid was increased almost 15-fold. The diagnose was acute porphyria, severe course, sensory-motor polyneuropathy, severe peripheral tetraparesis. The treatment was: glucose given treatment dosage of 100 g, then 250 g of dry matter during the day. Also appointed B vitamins (B1, B6, B12), alpha-lipoic acid 600 mg orally. The was a positive effect of the treatment. The muscle strength triceps muscle and the iliopsoas muscle became 5 points, the strength of the deltoid muscle increased significantly. The strength of the flexors of fingers also increased slightly. Consequently, for treatment of acute porphyria glucose effectively. Glucosa - inhibitor of synthetase enzyme i aminolevulinic acid. Glucose acts weaker arginate gem. Therefore, in the next stage of its inefficiency porphyria treatment prescribed heme arginate. In this case, glucose was effective. Appointment of haem arginate is not needed.

The complex polygenic testing for pregnancy planning stage to clarify the status of medium heavy and frequent mutations of monogenic diseases in a high and low risk groups. A survey algorithm is from genetic counseling to the diagnosis of embryos and fetuses. The application of this test in the field of assisted reproduction for donors in high-risk patients with consanguineous marriages. Comprehensive testing for mutation carrier is recommended for general prevention and can be assigned to all parents as effective measures of prevention of birth of children with severe monogenic disorders.

We report on a case of the prenatal ultrasound diagnosis of campomelic dysplasia at 12 wk of gestation. The ultrasound examination showed increased nuchal translucency and abnormally short and bowed legs. Pathological and histological studies confirmed the presence of campomelic dysplasia in the aborted fetus