Inverted duplication deletion 8p syndrome (inv dup del(8p)) is a rare chromosomal abnormality with a frequency of 1:10,000 – 30,000 newborns. Clinical manifestations of this syndrome include mental retardation, facial anomalies, hypoplasia/agenesis of corpus callosum, scoliosis and/or kyphosis, hypotonia, congenital heart defects.

Several models are proposed to explain the formation of inverted duplications adjacent to terminal deletions in the human genome. The features of inv dup del (8p) formation mechanisms and reported data on molecular cytogenetic characteristics of chromosomal rearrangement are considering in this review.

Fryns syndrome (FS, OMIM#194050) is a rare lethal autosomal recessive disorder with unknown genetic defect, manifested the distinct complex of the multiply congenital abnormalities (MCA), including diaphragmatic hernia. There was made the world literature overview for the FS phenotypic features, clinical and genealogical data of the published familial cases, ultrasound and morphological characteristics of affected fetuses.

Aim. Analysis of the clinical, morphological and prenatal ultrasound data of 12 FS cases, detected in Belarus during 2009-2018 years, and families’ reproduction results.

Material and methods. Genetic counseling of 10 families with affected outcome was performed. All the pregnants underwent the combined (biochemical and ultrasound) screening. Prenatal and postnatal cytogenetical studies (GTG-banding) and the morphological investigations of the 10 aborted fetuses and 2 deceased infants were fulfilled.

Results and Discussion. All the patients presented typical FS phenotypic features correlated with the diagnostic criteria. The spectrum of prenatal findings diagnosed at 1-st trimester included nuchal skin enlargement/cystic hygroma (5 cases), at the 2-ed trimester – diaphragmatic hernia (11 cases), omphalocele (1), other malformations (4 fetuses). The facial dysmorphisms (coarse face) were detected in all the patients. Lungs hypoplasia was found in all cases, 5 patients additionally dysplayed other abnormalities: pulmonary sequestration, cystic-adenomatoid malformation, lobular aplasia. Characteristic phalanges and nails hypoplasia or aplasia were registered in 11 cases, 3 sibs presented rare malformations – polydactyly (hands) and ectrodactyly (feet). Associated malformations spectrum included cleft palate, brain abnormalities (ventricular dilatation, arhinencephaly), cardiac defects, omphalocele, Meckel diverticule, hydronephroses, renal cysts, bicornuate uterus and hypospadia. The familial case with 3 affected sibs demonstrated a similarity in main diagnostic criteria. The couples reproduction analysis illulustrated a serious failure. Outcome of 29 pregnancies were as follows: 12 – FS cases, 4 – miscarries at 1-st trimester, 11 – healthy offspring and 2 cases – pregnancies are going on currently (both fetuses without malformations).

Conclusion. Clinical diagnosis of FS may be noted in patients (either fetuses or newborns), which display the conjunction of typical MCA pattern with a normal karyotype. Additional investigations must be used in order to exclude the associated abnormalities if diaphragmatic hernia has been detected in fetus. In our opinion polydactyly and ectrodactyly may be added to the FS phenotypic spectrum.

The aim of this investigation was to analyse the register of cystic fibrosis (CF) patients of Central Federal District (CFD) of Russian Federation (RF) in 2017. The register of CF patients includes data on 3096 people from 81 regions-entities of RF. CF patients in CFD represent 30% of total amount of patients included in the register. The full data presents 9 regions. The data of the rest 9 regions is presented partially. There is a list of genetically, clinical and microbiological peculiarities in comparison with RF in general and, at the same time, with other districts of CFD. The difference between adult patients and average age of patients by areas of received treatment, laboratory and instrumental indicators. There are obvious differences in infection indicators of the same age groups, there is difference in provided therapy. The analysis of the register data will enable to optimize aid to CF patients in CFD, to take over the experience of regions with the best indicators and criteria of the progress of the disease.

Using massively parallel sequencing, the COL1A1 and COL1A2 genes were analyzed in 16 patients from 10 families with osteogenesis imperfecta types I, III, and IV. To analyze the mutations in these genes, a panel of primers was developed for sequencing the complete gene sequence. As a result of the work, 10 mutations were revealed: six of them are in the COL1A1 gene, four mutations in the COL1A2 gene. All mutations, except one, were previously described in the literature and were found in patients with various types of osteogenesis imperfecta. Missense mutations were identified in five families, nonsense mutations in two families, splice site mutations in two cases, and a frameshift mutation in one patient. Unique mutations that were not repeated in unrelated patients were found in all families. The revealed high heterogeneity of the spectrum of mutations in the COL1A1 and COL1A2 genes in osteogenesis imperfecta indicates the effectiveness of using MPS-based methods for the diagnosis of this pathology.

Comorbidity of obstructive sleep apnea / hypopnea syndrome (OSAHS) and chronic obstructive pulmonary disease (COPD) is defined as overlap syndrome and is a state of mutual aggravation characterized by an accelerated development of pulmonary hypertension and chronic respiratory failure, as well as a high risk of sudden death in sleep. At the same time, obesity is one of the most significant and independent risk factors for the development of OSAHS. The aim of the study was to identify the role of the leptin receptor gene LEPR single nucleotide polymorphism (SNP) Q223R (rs1137101) in the development of overlap syndrome. A total of 134 people (73,1% of men and 26,9% of women) aged 60 [53; 65] years were examined, 66 of them with OSAHS, 30 patients with a diagnosis of COPD, and 38 with comorbidity of both forms of pathology. It was shown that the carriage of both the polymorphic G allele and the GG genotype is not a risk factor for the development of OSAHS in patients with COPD (p = 0,92) and does not correlate with the severity of both nosologies, but is statistically significantly associated with the formation of obesity 2 degrees (p < 0,05). The findings suggest that among the residents of the Krasnoyarsk Territory, the study of SNP Q223R of the LEPR gene cannot be used as a genetic predictor of the formation of overlap syndrome.