Two de novo UBR1 variants in trans as a cause of Johanson-Blizzard syndrome.

Aims/background: Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disease caused by pathogenic variants in the UBR1 gene. JBS is usually suspected based on characteristic anomalies, but only genetic testing provides a definitive diagnosis. Since most variants are inherited from the parents, we aimed to identify the causal variants in a Czech proband with clinically suspected JBS and perform segregation analysis.

The guidelines for clinical practice for carriers of germline mutations in the Lynch syndrome predisposition genes MLH1, MSH2, MSH6, PMS2 and large deletions of EPCAM (4.2024).

The guidelines for clinical practice for carriers of pathogenic variants in clinically relevant genes predisposing to Lynch syndrome and colorectal cancer define the steps of primary and secondary prevention that should be provided to the individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E.

The guidelines for clinical practice for carriers of germline mutations in hereditary breast, ovarian, prostate, and pancreatic cancer predisposition genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 (4.2024).

The Guidelines for Clinical Practice for carriers of pathogenic variants in clinically relevant cancer predisposition genes define the steps of primary and secondary prevention that should be provided to these individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E.

A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition.

Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.

A recurrent synonymous L1CAM variant in a fetus with hydrocephalus.

We report the case of a hydrocephalic fetus in which clinical exome sequencing revealed a recurrent synonymous variant of unknown significance, c.453G>T, in the L1CAM gene. This report presents the second case of X-linked hydrocephalus in a fetus with this variant.

Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus.

Background: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing.

Genetic Predisposition to Male Breast Cancer.

Male breast cancer (mBC) is a rare cancer diagnosis that constitutes less than 1 % of all breast cancer cases globally. Genetic factors play an important role in the mBC risk. Germline pathogenic variants (PVs) in cancer predisposition genes could be identified in about 15 % of cases.

Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines.

Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). The current European urology guidelines recommend screening for LS in patients with UTUC up to the age of 60 years. In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current guidelines in detecting LS.

Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study.

Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening.

Germline multigene panel testing of patients with endometrial cancer.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. The present study aimed to determine the frequency of germline pathogenic variants (PV) in patients with EC. In this multicenter retrospective cohort study, germline genetic testing (GGT) was performed in 527 patients with EC using a next generation sequencing panel targeting 226 genes, including 5 Lynch syndrome (LS) and 14 hereditary breast and ovarian cancer (HBOC) predisposition genes, and 207 candidate predisposition genes.

Cystic ovarian teratoma as a novel tumor and growth hormone deficiency as a new condition presenting in Multiple Endocrine Neoplasia type 2B: Case reports and review of the literature.

Background: We describe early and typical nonendocrine symptoms of Multiple Endocrine Neoplasia type 2B (MEN2B) presented in our patients with de novo M918T mutation in the RET proto-oncogene in early childhood, however, the diagnosis of MEN2B and medullary thyroid carcinoma (MTC) was confirmed late, in the second decade of life. In this paper, we emphasize the possibility of growth retardation, growth hormone (GH) deficiency and ovarian teratoma as a new symptom of MEN2B.

Case Reports: Advanced MTC with palpable mass on the neck and nonendocrine symptoms such as marfanoid habitus, thickened lips, mucosal neuromas led to the diagnosis in case 1 at the age of 13 years and GH deficiency and nonendocrine symptoms in case 2 at the age of 11 years.

Prevalence of cancer in patients with superficial vein thrombosis and its clinical importance.

Objective: The objective of the present study was to evaluate the prevalence of cancer in patients with superficial vein thrombosis (SVT) of the legs. Moreover, we evaluated the potential determinants of SVT complications by comparing a subgroup with isolated SVT and a subgroup of SVT complicated by concurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) with respect to the presence of cancer and other clinical and laboratory characteristics.

Methods: The present single-center, retrospective study of prospectively collected data was conducted in a tertiary care setting.

Unique characteristics of informed consent in clinical genetics and genetic counselling.

Rapid development of clinical genetics was enabled by the advances of molecular genetic laboratory diagnostics. Genetic laboratory testing has unique characteristics, and results of germinal genome testing has consequences not only for the patient but also for his relatives. Genetic laboratory testing in the Czech Republic is governed by the act no.

Precise determination of primary cytogenetic abnormalities provides added value for stratification of chronic lymphocytic leukemia patients.

Cytogenetic analysis has become a standard procedure in the management of newly diagnosed chronic lymphocytic leukemia patients. Prognostic information is reported based on the presence of certain abnormalities and karyotype complexity after conventional karyotyping and/or fluorescence in situ hybridization (FISH). The information on cytogenetic abnormalities occurring in isolation is robust; however, the performance of patients with two or more cytogenetic abnormalities is heterogeneous and information is scarce.

Late diagnosis of complete androgen insensitivity syndrome and transmission/carriers of the condition in a family with mutation c.2495G> T p.(Arg832Leu) in exon 7 of the androgen receptor gene: genetic, clinical and ethical aspects.

Background: The complete androgen insensitivity syndrome (CAIS) is a rare genetic disorder causing insensitivity to androgens in a person with female phenotype and 46,XY karyotype due to a mutation in the androgen receptor gene located on chromosome X. These children are born with female external genitalia, and females are transmitters.

Case Report: We illustrate an unexpected diagnosis of CAIS in two siblings during examination for short stature, and describe transmission/carriers in the family along with ethical aspects.

First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide.

Thrombophilia testing results in patients with a first venous thromboembolic event: should the selection criteria for testing be revisited?

Background: After the first episode of venous thromboembolism (VTE), the guidelines recommend selective thrombophilia testing and suggest not to test the patients older than 40 years with a provoked event and all patients above 60.

Methods: We compared thrombophilia workup results in 544 patients, meeting or not meeting the selection criteria. Homozygous factor V Leiden or prothrombin gene mutation, natural anticoagulant deficiencies, antiphospholipid syndrome or combination of ≥2 disorders were considered a strong thrombophilia.

First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic.

We characterized a case of congenital adrenal insufficiency caused by cholesterol side-chain cleavage enzyme (P450scc) deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. We confirmed primary adrenal insufficiency.

Allogeneic stem cell transplantation can improve outcome of AML patients without complete cytogenetic response after induction and consolidation treatment.

Unlabelled: Our retrospective analysis was performed on 376 consecutive patients diagnosed with AML. A total of 256 (68%) were treated with standard "7+3" induction and high-dose cytarabine and mitoxantrone containing "4+3" consolidation/intensification regimens. Our study focused on patients with presumably very poor prognosis - patients, who did not achieve complete cytogenetic remission (CRc).

The association of factor V Leiden with various clinical patterns of venous thromboembolism-the factor V Leiden paradox.

Background: Factor V Leiden (FVL) supposedly carries relatively higher risk of deep vein thrombosis (DVT), compared to the risk of pulmonary embolism (PE).

Aim: To prove this paradox in a group of patients with various clinical presentation of venous thromboembolism (VTE).

Materials And Methods: We retrospectively evaluated clinical pattern of VTE in patients who had been referred to vascular clinic shortly after an acute VTE event.

The translocation t(2;11)(p21;q23) without MLL gene rearrangement--a possible marker of good prognosis in myelodysplastic syndrome patients.

The translocation t(2;11)(p21;q23) is associated with de novo myelodysplastic syndromes (MDS) and has an overall frequency of approximately 1%. The outcome of MDS patients with this translocation is not clear until now, because most of the clinical data addressing the t(2;11)(p21;q23) has been collected without investigating the status of the mixed lineage leukemia (MLL) gene. In this report, we present seven new patients with MDS diagnosis and the t(2;11)(p21;q23) in bone marrow cells; all of them without MLL gene rearrangement.

Deep vein thrombosis and/or pulmonary embolism concurrent with superficial vein thrombosis of the legs: cross-sectional single center study of prevalence and risk factors.

Aim: The aim of this paper was to assess the prevalence of concurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the patients with superficial vein thrombosis (SVT) of the legs and to find factors significantly and independently associated with coincident DVT/PE.

Methods: In the setting of a tertiary referral hospital, patients with SVT, attending vascular clinic, underwent physical examination, laboratory testing and leg vein ultrasound (in the case of clinically suspected PE also perfusion/ventilation lung scan or/and helical CT pulmonary angiography). In statistical analysis, we used unpaired t-test, non-parametric Wilcoxon rank sum test, stepwise logistic regression and multivariable logistic regression model.

Recurrent pregnancy loss, plasminogen activator inhibitor-1 (-675) 4G/5G polymorphism and antiphospholipid antibodies in Czech women.

Problem: This study compares the frequencies of plasminogen activator inhibitor-1 (-675) 4G/5G polymorphism and its relationship with eight antiphospholipid antibodies (aPLs) in serum of 157 patients with repeated pregnancy loss (RPL).

Method Of Study: PAI-1 (-675) 4G/5G polymorphism was determined using standard PCR-RFLP method. Enzyme-linked immunosorbent assay was used for the detection of aPLs against ph-serine, ph-ethanolamine, ph-inositol, ph-DL-glycerol, phosphatidic acid, annexin V, cardiolipin, and beta2-GPI.