Background Bosnia and Herzegovina is among ten countries in the world with the highest mortality rate due to COVID-19. Lack of lockdown, open borders, high mortality rate, no vaccination plan, and strong domestic anti-vaccination movement present serious COVID-19 concerns in Bosnia and Herzegovina. In such circumstances, we set out to study 1) the willingness of general public to receive the vaccine, 2) factors that affect vaccine rejection, and 3) motivation for vaccine acceptance. Methods A cross-sectional study was conducted among 10471 adults in Bosnia and Herzegovina to assess the acceptance or rejection of participants toward COVID-19 vaccination. Using a logistic regression model, we examined the associations of sociodemographic characteristics with vaccine rejection, reasons for vaccine hesitancy, preferred vaccine manufacturer, and information sources. Results Surprisingly, only 25.7% of respondents indicated they would like to get a COVID-19 vaccine, while 74.3% of respondents were either hesitant or completely rejected vaccination. The vaccine acceptance increased with increasing age, education, and income level. Major motivation of pro-vaccination behavior was intention to achieve collective immunity (30.1%), while the leading incentive for vaccine refusal was deficiency of clinical data (30.2%). The Pfizer-BioNTech vaccine is shown to be eightfold more preferred vaccine compared to the other manufacturers. For the first time in Bosnia, vaccine acceptance among health care professionals has been reported, where only 39.4% of healthcare professionals expressed willingness to get vaccinated. Conclusion With the high share of the population unwilling to vaccinate, governmental impotence in securing the vaccines supplies, combined with the lack of any lockdown measures suggests that Bosnia and Herzegovina is unlikely to put COVID-19 pandemic under control in near future.

Introduction: Rapid-onset obesity, hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) is a rare syndrome beginning at 3-6 years of age with approximately 150 cases described. Additional features include eye abnormalities, neurobehavioral dysfunction and paraneoplastic tumors. The etiology of the complex phenotype remains unknown. Methods: This study aims to investigate the genetic landscape of this complex phenotype by whole exome sequencing (WES) and copy number variation (CNV) analysis. We recruited 33 families (27 trios, 1 duo and 5 singletons) with a proband with ROHHAD syndrome (Ize-Ludlow 2007, Pediatrics). WES of 89 individuals was performed at the Center for Mendelian Genomics, Broad Institute. The Illumina platform with a mean coverage of ~100X (> 90% targets 20x) and Infinium Global Screening Array BeadChip 24v1.0 were used. Results: This report includes 28 probands (female = 18, 64%) with rapid onset obesity (100%), hypoventilation (88%), hypothalamic dysfunction (69%), eye disorders (62%) and neurobehavioral abnormalities (76%). Neuroendocrine tumor, ganglioneuroblastoma, was present in 38% (n=13). No unifying causative single gene or CNV was identified, but a number of sequence variants are prioritized. ARNT2, which encodes for a helix-loop-helix transcription factor, plays a role in the development of the hypothalamic-pituitary axis, postnatal brain growth, and visual and renal function. The de novo monoallelic missense variant was found in a 14-year old white girl (BMIz +3.25) with extreme obesity and a neurobehavioral phenotype. OCRL1, a multi-domain protein involved in cytoskeleton-plasma membrane adhesion, endosomal trafficking and in primary cilium assembly. Mutations in this gene have also been known to cause Lowe syndrome. A hemizygous X-linked frameshift variant in a 5-year old white boy with extreme obesity (BMIz +5.48), central hypoventilation neurobehavioral dysfunction and ganglioneuroblastoma. A monoallelic missense variant in NSD1, a transcriptional intermediary factor acting as a histone methyltransferase, was identified in a 8-year old Hispanic girl with severe obesity (BMIz +2.91), neurobehavioral disorder, pituitary and eye dysfunction and ganglioneuroblastoma. NSD1 is known to cause Sotos and Beckwith-Wiedemann. Compound heterozygous variants in KIF7, a key component of the Hedgehog signaling pathway, were identified in a 14-year old white girl with severe obesity (BMIz +3.00), autistic behavior, pituitary dysfunction and central hypoventilation. This gene is known to cause autosomal recessive hydrolethalis and acroscallosal syndromes with mutations also noted in Bardet-Biedl, Meckel and Joubert syndromes. Conclusion: While no unifying genetic cause has been identified in ROHHAD syndrome, it is possible that the phenotype represents a collection of complex genetic syndromes.

Here we describe the major genetic and genomic aberrations found in myeloid malignancies and how those markers are used in patients' diagnosis, prognosis, and targeted treatment. In Bosnia and Herzegovina, cytogenetic and molecular diagnostics for myeloid malignancies have been established and continually improved since 2005. We report the current state of available diagnostic tools for myeloid malignancies in Bosnia and Herzegovina. Myeloid malignancies are a heterogeneous group of clonal blood diseases characterized by defects in hematopoietic stem cells and myeloid progenitors that lead to abnormal proliferation, differentiation, localization, and self-renewal. Most common myeloid malignancies include myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Molecular diagnostics of myeloid malignancies have significantly expanded in the last decade with new genetic and genomic markers for diagnosis, prognosis, and treatment. CONCLUSION: In the last decade, several new genomic markers important for patient diagnosis, prognosis, and therapy have been discovered that need to be implemented in routine molecular diagnostics not only in developed nations but also in developing nations such as Bosnia and Herzegovina.

Heart failure is a leading cause of morbidity and mortality. Around 4% of patients with heart failure carry a pathogenic genetic aberration that causes cardiomyopathy and subsequently leads to heart failure. There are five types of primary genetic cardiomyopathies that can give rise to heart failure: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, arrhythmogenic cardiomyopathy (ACM), restrictive cardiomyopathy (RCM), and left ventricular noncompaction (LVNC). If genetic cardiomyopathy is suspected, genomic/genetic testing is recommended because it provides the underlying cause for the diagnosis, prognostic parameters, and possibility to test family members at risk. Testing should be conducted as part of a multidisciplinary approach by a team of adult or paediatric cardiologists, geneticists, and genetic counsellors. Here we will discuss 1) different genomic testing approaches and the management of variants of uncertain significance, 2) management of patients with suspected genetic cardiomyopathy in a multidisciplinary team, and 3) the associations between genotypes and phenotypes of most commonly mutated genes such as MYH7, TNNT2, TPM1, MYBPC3, TTN, and others. In conclusion, genetic testing of patients with cardiomyopathies helps with proper diagnosis, prognosis, treatment, and identification of relatives at risk.

During a pandemic, mitigation as well as protection of system-critical or vulnerable institutions requires massive parallel, yet cost effective testing to monitor the spread of agents such as the current SARS-CoV2 virus. Here we present SARSeq, saliva analysis by RNA sequencing, as an approach to monitor presence of SARS-CoV2 and other respiratory viruses performed on tens of thousands of samples in parallel. SARSeq is based on next generation sequencing of multiple amplicons generated in parallel in a multiplexed RT-PCR reaction. It relies on a two-dimensional unique dual indexing strategy using four indices in total for unambiguous and scalable assignment of reads to individual samples. We calibrated this method using dilutions of synthetic RNA and virions to show sensitivity down to few molecules, and applied it to hundreds of patient samples validating robust performance across various sample types. Double blinded benchmarking to gold-standard quantitative RT-PCR performed in a clinical setting and a human diagnostics laboratory showed robust performance up to a Ct of 36. The false positive rate, likely due to cross contamination during sample pipetting, was estimated at 0.04-0.1%. In addition to SARS-CoV2, SARSeq detects Influenza A and B viruses as well as human rhinovirus and can be easily expanded to include detection of other pathogens. In sum, SARSeq is an ideal platform for differential diagnostic of respiratory diseases at a scale, as is required during a pandemic.