The Role of Next-Generation Sequencing in the Management of Patients with Suspected Non-Ischemic Cardiomyopathy after Syncope or Termination of Sudden Arrhythmic Death.

Cardiac arrhythmias and sudden death are frequent in patients with non-ischemic cardiomyopathy and can precede heart failure or additional symptoms where malignant cardiac arrhythmias are mostly the consequence of advanced cardiomyopathy and heart failure. Finding these subgroups and making an early diagnosis could be lifesaving. In our retrospective study, we are presenting arrhythmic types of frequent cardiomyopathies where an arrhythmogenic substrate is less well defined, as in ischemic or structural heart disease.

Identification of potentially pathogenic variants for autism spectrum disorders using gene-burden analysis.

Gene- burden analyses have lately become a very successful way for the identification of genes carrying risk variants underlying the analysed disease. This approach is also suitable for complex disorders like autism spectrum disorder (ASD). The gene-burden analysis using Testing Rare Variants with Public Data (TRAPD) software was conducted on whole exome sequencing data of Slovenian patients with ASD to determine potentially novel disease risk variants in known ASD-associated genes as well as in others.

Impaired Neurodevelopmental Genes in Slovenian Autistic Children Elucidate the Comorbidity of Autism With Other Developmental Disorders.

Autism spectrum disorders (ASD) represent a phenotypically heterogeneous group of patients that strongly intertwine with other neurodevelopmental disorders (NDDs), with genetics playing a significant role in their etiology. Whole exome sequencing (WES) has become predominant in molecular diagnostics for ASD by considerably increasing the diagnostic yield. However, the proportion of undiagnosed patients still remains high due to complex clinical presentation, reduced penetrance, and lack of segregation analysis or clinical information.

Clinical Evaluation of Two Non-Invasive Genetic Tests for Detection and Monitoring of Urothelial Carcinoma: Validation of UroVysion and Xpert Bladder Cancer Detection Test.

A variety of commercially available urinary molecular markers have been introduced for detecting and monitoring urothelial carcinoma (UC). We prospectively evaluated the UroVysion Bladder Cancer Kit (FISH) and the Xpert® Bladder Cancer Detection (Xpert) test. Both tests were performed on voided urine samples after negative cystoscopy and negative abdominal ultrasound (US) and/or negative computed tomography urography (CTU).

CNVs and Chromosomal Aneuploidy in Patients With Early-Onset Schizophrenia and Bipolar Disorder: Genotype-Phenotype Associations.

Early-onset schizophrenia (EOS) and bipolar disorder (EOB) start before the age of 18 years and have a more severe clinical course, a worse prognosis, and a greater genetic loading compared to the late-onset forms. Copy number variations (CNVs) are an important genetic factor in the etiology of psychiatric disorders. Therefore, this study aimed to analyze CNVs in patients with EOS and EOB and to establish genotype-phenotype relationships for contiguous gene syndromes or genes affected by identified CNVs.

Copy number variant discrepancy resolution using the ClinGen dosage sensitivity map results in updated clinical interpretations in ClinVar.

Conflict resolution in genomic variant interpretation is a critical step toward improving patient care. Evaluating interpretation discrepancies in copy number variants (CNVs) typically involves assessing overlapping genomic content with focus on genes/regions that may be subject to dosage sensitivity (haploinsufficiency (HI) and/or triplosensitivity (TS)). CNVs containing dosage sensitive genes/regions are generally interpreted as "likely pathogenic" (LP) or "pathogenic" (P), and CNVs involving the same known dosage sensitive gene(s) should receive the same clinical interpretation.

A mosaic form of microphthalmia with linear skin defects.

Background: Microphthalmia with linear skin defects (MLS) syndrome is a rare neurodevelopmental X-dominant disorder. It presents in females as it is normally lethal in males. Three causative genes for MLS syndrome (OMIM 309801) have been identified all taking part in mitochondrial respiratory chain and oxidative phosphorylation.

Rare structural variants in the DOCK8 gene identified in a cohort of 439 patients with neurodevelopmental disorders.

Detection of copy number variations (CNVs) is a first-tier clinical diagnostic test for children with neurodevelopmental disorders (NDD), which reveals the genetic cause of the disorder in more than 20%. These are mostly known microdeletion/microduplication syndromes, but variants of unknown clinical significance (VOUS) and ambiguous CNVs can also be detected. An example of the last two are abnormalities in the DOCK8 gene.

Identification of genomic copy number variations associated with specific clinical features of head and neck cancer.

Background: Copy number variations (CNSs) of large genomic regions are an important mechanism implicated in the development of head and neck cancer, however, for most changes their exact role is not well understood. The aim of this study was to find possible associations between gains/losses of genomic regions and clinically distinct subgroups of head and neck cancer patients.

Results: Array comparative genomic hybridization (aCGH) analysis was performed on DNA samples in 64 patients with cancer in oral cavity, oropharynx or hypopharynx.

Impact of prenatal screening on the prevalence of Down syndrome in Slovenia.

Objectives: To evaluate the impact of prenatal screening and genetic testing for trisomy 21 (T21) on the prevalence of T21 in Slovenia.

Design And Setting: Data about all prenatally and postnatally confirmed cases of T21 in Slovenia between 1981 and 2012 were collected retrospectively from all genetic laboratories in Slovenia. The expected number of babies with T21 according to maternal age was calculated.

TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer.

Background: TMPRSS2:ERG gene aberration may be a novel marker that improves risk stratification of prostate cancer before definitive cancer therapy, but studies have been inconclusive.

Methods: The study cohort consisted of 202 operable prostate cancer Slovenian patients who underwent laparoscopic radical prostatectomy. We retrospectively constructed tissue microarrays of their prostatic specimens for fluorescence in situ hybridization, with appropriate signals obtained in 148 patients for subsequent statistical analyses.

Specific behavioural phenotype and secondary cognitive decline as a result of an 8.6 Mb deletion of 2q32.2q33.1.

Chromosomal abnormalities involving 2q32q33 deletions are very rare and present with a specific phenotype. This case report describes a 37-year-old female patient with 2q32q33 microdeletion syndrome presenting with the characteristic features, but with the addition of secondary cognitive decline. Molecular karyotyping was performed on the patient and her parents.

Predictive value of paroxysmal EEG abnormalities for future epilepsy in focal febrile seizures.

Purpose Of The Study: To reassess the predictive role of clinical parameters and epileptiform paroxysmal EEG abnormalities for subsequent epilepsy in patients with febrile seizures.

Patients And Methods: 179 patients with febrile seizures were included in a prospective study investigating the impact of some clinical parameters and EEG abnormalities that could be important for future epilepsy. EEGs were performed in afebrile patients after hospital discharge.

A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5.

Background: Rearrangements involving chromosome 5p often result in two syndromes, Cri-du-chat (CdC) and Trisomy 5p, caused by a deletion and duplication, respectively. The 5p15.2 has been defined as a critical region for CdC syndrome; however, genotype-phenotype studies allowed isolation of particular characteristics such as speech delay, cat-like cry and mental retardation, caused by distinct deletions of 5p.

An evaluation of SOX2 and hTERC gene amplifications as screening markers in oral and oropharyngeal squamous cell carcinomas.

Background: Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers. The poor survival rate among oral cancer patients can be attributed to several factors, one of them being lack of early detection. A key approach to this problem would be to detect potentially malignant lesion at their early stage.

Slovenian five-year experiences with rapid prenatal diagnosis of common chromosome aneuploidies using quantitative-fluorescence polymerase chain reaction.

Objective: Quantitative-fluorescence polymerase chain reaction (QF-PCR) was used to detect common fetal aneuploidies in pregnancies with increased (maternal age) or high risk (increased nuchal translucency, abnormal fetal ultrasonography, positive biochemical hormone test, or positive family history) for fetal aneuploidy.

Methods: The QF-PCR testing was performed on 642 prenatal samples (73.3% amniotic fluids, 26.

Submicroscopic interstitial deletion of chromosome 11q22.3 in a girl with mild mental retardation and facial dysmorphism: Case report.

Background: Except for terminal deletions that lead to Jacobsen syndrome, interstitial deletions involving the long arm of chromosome 11 are not frequently reported. A clinically distinct phenotype is usually observed in these cases, and no clear genotype-phenotype correlation is proposed.

Results: Here we present a case study of a 5-year-old girl with de novo submicroscopic deletion of chromosome 11q22.

Is the JAK2 V617F mutation a hallmark for different forms of thrombosis?

Background/aims: The association between venous thrombosis outside the splanchnic area as well arterial thromboembolism and the JAK2 V617F mutation, an important marker for chronic myeloproliferative neoplasms (MPN), is not completely clear.

Methods: Four hundred forty-four patients with venous thrombosis of the lower/upper limbs and/or pulmonary embolism and 60 patients with ischemic stroke were screened for the JAK2 V617F mutation, factor V Leiden, and factor II G20210A.

Results: The JAK2 V617F mutation was detected in 1.

Screening of TERC gene amplification as an additional genetic diagnostic test in detection of cervical preneoplastic lesions.

TERC gene amplification was investigated as a possible diagnostic marker for use in routine cytological screening to improve the accuracy of conventional screening procedures in detection of cervical preneoplastic lesions. Cervical smears were screened and classified as low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). A fluorescence in situ hybridization procedure using a TERC-specific DNA probe was performed on the same specimens and TERC gene copy number was evaluated.

How safe is germinal vesicle stage oocyte rescue? Aneuploidy analysis of in vitro matured oocytes.

Objective: To evaluate the rate and type of aneuploidies of chromosomes 13, 16, 18, 21 and 22, with respect to the length of in vitro maturation (IVM) period, and to compare the results to previously published studies on aneuploidy rates of unfertilized, uninseminated mature oocytes and first polar bodies.

Study Design: Two hundred and twelve immature germinal vesicle stage oocytes were assigned to two groups. After successful IVM, depending on their maturational period of 24h (Group A) or 36h (Group B), chromosomal analysis was performed by five color fluorescence in situ hybridization (FISH).

Subtelomeric chromosome rearrangements in children with idiopathic mental retardation: applicability of three molecular-cytogenetic methods.

Aim: To identify cryptic subtelomeric rearrangement, a possible cause of idiopathic mental retardation by means of multiprobe telomere fluorescent in situ hybridization (T-FISH).

Methods: Hundred patients (median age 3.0 years) with mental retardation and dysmorphic features were screened using specific T-FISH probes.