Background: Congenital skeletal abnormalities are a heterogeneous group of diseases most commonly associated with small or disproportionate growth, cranial and facial dysmorphisms, delayed bone maturation, etc. None-theless, no detailed genotype-phenotype correlation in patients with specific genetic variants is readily available. Ergo, this study focuses on the analysis of patient phenotypes with candidate variants in genes involved in bone growth as detected by molecular genetic analysis. Methods: In this study we used molecular genetic methods to analyse the ACAN, COL2A1, FGFR3, IGFALS, IGF1, IGF1R, GHR, NPR2, STAT5B and SHOX genes in 128 Czech children with suspected congenital skeletal abnor-malities. Pathogenic variants and variants of unclear clinical significance were identified and we compared their frequency in this study cohort to the European non-Finnish population. Furthermore, a prediction tool was utilised to determine their possible impact on the final protein. All clinical patient data was obtained during pre-test genetic counselling. Results: Pathogenic variants were identified in the FGFR3, GHR, COL2A1 and SHOX genes in a total of six pa-tients. Furthermore, we identified 23 variants with unclear clinical significance and high allelic frequency in this cohort of patients with skeletal abnormalities. Five of them have not yet been reported in the scientific literature. Conclusion: Congenital skeletal abnormalities may lead to a number of musculoskeletal, neurological, cardio-vascular problems. Knowledge of specific pathogenic variants may help us in therapeutic procedures.

As part of the implementation and validation of an optimal diagnostic approach based on high-throughput sequencing by Ion Torrent platform in the diagnosis of the rare thrombophilic conditions of protein S (PS), protein C (PC) and antithrombin (AT) deficiency, we compared data from three different software tools – Torrent Suite, Ion Reporter and NextGene – to compare their performance and accuracy in the analysis of each sequence variant detected. A cohort of 31 patients was selected for PS (7), PC (13) and AT (11) deficiency based on defined indication criteria. Within these patient groups, a mutation detection rate of 67.7 For data generated from the Ion Torrent platform, software from the same provider seems to be more suitable, mainly because of the quality of the false positive filtering. For further evaluation of the validity of the software used, it will be necessary to expand the cohort of patients examined.

OBJECTIVE Summary of knowledge in the field of ovarian cancer and genetic predisposition. RESULTS Ovarian tumors are usually diagnosed at advanced stages of the disease and the prognosis for these patients is generally poor. The 5-year overall survival rate, regardless of the histopathological type of tumor, is around 44%. Germline mutations causing hereditary tumor syndromes are predominantly involved in the development of epithelial ovarian tumors. The most common is hereditary breast and ovarian cancer syndrome, which is caused by germline mutations in the tumor suppressor genes BRCA1 and BRCA2. Several other tumor suppressor genes and oncogenes are known to be associated with ovarian tumors and cause other types of tumor syndromes. Inherited tumor syndromes include Lynch syndrome, Peutz-Jegers syndrome, Gorlin syndrome, Li-Fraumeni syndrome and others. The indication for genetic examination of germline mutations is given by a clinical geneticist on the basis of the recommendation of the attending physician. At present, every ovarian tumor, primary peritoneal tumor and tube tumor diagnosed at any age is indicated for genetic testing. CONCLUSION Early identification of genes for hereditary cancer syndromes, thanks to rapidly developing molecular genetic methods, is an important step towards personalized treatment of ovarian cancer and preventive measures in families at risk. It is also important to note that a negative molecular genetic test result does not exclude genetic risk.

Turner syndrome (TS) is caused by the absence or structural abnormality of X chromosome. Compared with the general population, the prevalence of congenital heart defects is significantly higher in women with TS, especially with 45,X karyotype. Moreover, congenital heart defects represent the major risk for aortic dissection in TS individuals. There is a lack of reliable evidence whether the extremely variable cardiovascular phenotype including presence of aortic coarctation (CoA) and bicuspid aortic valve (BAV) in TS women may be influenced by the parental origin of the retained X chromosome. DNA samples were collected from peripheral lymphocytes of 48 women with non-mosaic 45,X karyotype and from buccal swab of their biological parents' cheek. Subsequently, the single normal X-chromosome origin was identified. Based on genetic evaluation, patients were divided into two subgroups according to the parenteral original of X chromosome - maternal (XM), and paternal (XP). Complete cardiovascular examination (echocardiography, MRI of the heart and great vessels) was performed in each of our study patient. Differences between the prevalence of BAV and CoA in two above mentioned subgroups were tested by Student's t-test using R Statistical Software version 2.15.3. The origin of the single X chromosome was as follows: in 14 (29.2%) individuals was proved paternal and in 34 (70.8%) maternal origin of X chromosome. The prevalence of BAV in the whole group was 47.9%, in XP 58%, in XM 44.1%; the prevalence of CoA in the whole group was 8.3%, in XP 7.1%, in XM 8.8%. There was no statistically significant difference identified between the prevalence of BAV and CoA in XP and XM subgroups. Our study confirmed an extremely high prevalence of BAV and CoA in non-mosaic women with X chromosome monosomy but no clear evidence for X-linked genomic imprinting effect on the CoA and BAV development in TS individuals was found. However, further studies of larger numbers of TS patients are crucial to finally clarify the real relationship of genomic imprinting and cardiovascular disease in TS. Type of funding source: Public grant(s) – National budget only. Main funding source(s): Supported by the grant from Ministry of Health of the Czech Republic VES 2017