Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

• MeSH
• dospělí MeSH
• epigeneze genetická MeSH
• epigenomika MeSH
• fúze genů * MeSH
• genetická predispozice k nemoci MeSH
• genomika MeSH
• imunohistochemie MeSH
• jednonukleotidový polymorfismus MeSH
• juxtaglomerulární aparát patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• nádorové biomarkery * genetika   MeSH
• nádory ledvin * genetika   patologie   chemie   MeSH
• sekvenování celého genomu MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis.

• MeSH
• ATM protein genetika   MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• infekce papilomavirem MeSH
• inhibitor p16 cyklin-dependentní kinasy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory penisu * genetika   mortalita   patologie   virologie   MeSH
• prognóza MeSH
• proteiny vázající telomery MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shelterinový komplex MeSH
• spinocelulární karcinom * genetika   mortalita   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome, or panel sequencing data sets aligned to a GRCh37, GRCh38, or T2T reference genome. METHODS: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs. It uses these reads to determine whether an individual most likely has 0 functional copies of SMN1. RESULTS: We developed SMA Finder and evaluated it on 16,626 exomes and 3911 genomes from the Broad Institute Center for Mendelian Genomics, 1157 exomes and 8762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank. SMA Finder's false-positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true-positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as limb-girdle muscular dystrophy. CONCLUSION: Our extensive evaluation of SMA Finder on exome, genome, and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, and the existence of treatment options, we propose that it is time to add SMN1 to the American College of Medical Genetics list of genes with reportable secondary findings after genome and exome sequencing.

• MeSH
• algoritmy MeSH
• exom genetika   MeSH
• genom lidský genetika   MeSH
• genomika metody   MeSH
• lidé MeSH
• protein přežití motorických neuronů 1 genetika   MeSH
• protein přežití motorických neuronů 2 genetika   MeSH
• sekvenční analýza DNA metody   MeSH
• sekvenování exomu MeSH
• spinální svalová atrofie * genetika   diagnóza   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. METHODS: Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. RESULTS: A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. CONCLUSION: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.

• MeSH
• algoritmy MeSH
• dítě MeSH
• genetické testování * metody   MeSH
• lidé MeSH
• mladiství MeSH
• mutace genetika   MeSH
• nanismus genetika   diagnóza   MeSH
• pokrevní příbuzenství * MeSH
• poruchy růstu genetika   diagnóza   MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvenování exomu metody   MeSH
• tělesná výška genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Irák MeSH

Necrotizing enterocolitis (NEC) is one of the most devastating intestinal diseases observed in preterm in the first days of life. Researchers have recently focused on potential predictive biomarkers for early and concomitant diagnoses. Thus, we inquired about the linkage of intestinal dysbiosis, one of the most important factors in NEC development to the gut microbiota. In this study, the systematic differences in the bacterial composition between neonates affected by NEC and healthy newborns were highlighted by metagenomic analysis. The next-generation sequencing of the V3-V4 variable region of the 16S rRNA gene and gene-specific qPCR analyzed the untargeted gut microbiota. Total bacteria, total and fecal coliform loads in stool samples with NEC were higher than control. OTU-level relative abundances of NEC infant was characterized by Firmicutes and Bacteroidetes at phylum levels. At the genus level, NEC stool was identified by the lack of Klebsiella and the presence of Roseburia, Blautia, and Parasutterella. Finally, Clostridium fessum was the predominant species of Clostridium genus in disease and healthy specimens at the species level, whereas Clostridium jeddahitimonense was at NEC diagnosis. Despite a strong relationship between pathophysiology and characterization of gut microbiota at a clinical diagnosis of NEC, our results emphasize the broad difficulty in identifying potential biomarkers.

• MeSH
• Bacteria * klasifikace   genetika   izolace a purifikace   MeSH
• DNA bakterií genetika   MeSH
• dysbióza mikrobiologie   MeSH
• feces * mikrobiologie   MeSH
• lidé MeSH
• metagenomika MeSH
• nekrotizující enterokolitida * mikrobiologie   MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• RNA ribozomální 16S * genetika   MeSH
• střevní mikroflóra * MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Phenopacket Store v.0.1.19 includes 6,668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3,834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

• MeSH
• algoritmy MeSH
• databáze genetické MeSH
• fenotyp * MeSH
• genomika * metody   MeSH
• lidé MeSH
• software * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A novel Gram-stain-negative, strictly aerobic, rod-shaped, light-yellow-pigmented, and chemo-organoheterotrophic bacterium, designated DF-77T, was isolated from dense mats of filamentous algae collected in March 2004 at Okinawa in Japan. The microorganism grew at 0-2.0% NaCl concentrations (w/v), pH 6.0-9.0, and 20-30 °C. The 16S rRNA gene sequence-based phylogenetic tree demonstrated that the strain DF-77T is a novel member of the family Flavobacteriaceae and was greatly related to Flagellimonas nanhaiensis SM1704T with sequence similarity of 95.5%. The main fatty acids were iso-C15:1 G, iso-C15:0, and iso-C17:0 3-OH, and the only isoprenoid quinone was menaquinone-6. The dominant polar lipids were phosphatidylethanolamine, two unidentified aminolipids, an unidentified phosphoaminolipid, and four unidentified lipids. The genome size of strain DF-77T was 3.60 Mbp with a DNA G + C content of 47.5%. The average nucleotide identity (ANI) value between the genomes of strain DF-77T and its closely related species was 69.8-70.7%. The digital DNA - DNA hybridization (dDDH) value of strain DF-77T with the strain of F. nanhaiensis SM1704T was 16.8%. The genome of the strain DF-77T revealed that it encoded several genes involved in bio-macromolecule degradation, indicating a high potential for producing industrially useful enzymes. Consequently, the strain is described as a new species in the genus Flagellimonas, for which the name Flagellimonas algarum sp. nov., is proposed with the type strain DF-77T (= KCTC 72791T = NBRC 114251T).

• MeSH
• DNA bakterií genetika   chemie   MeSH
• Flavobacteriaceae * klasifikace   izolace a purifikace   genetika   MeSH
• fosfolipidy analýza   MeSH
• fylogeneze MeSH
• genom bakteriální MeSH
• hybridizace nukleových kyselin MeSH
• mastné kyseliny analýza   MeSH
• RNA ribozomální 16S genetika   MeSH
• sekvenční analýza DNA MeSH
• techniky typizace bakterií MeSH
• vitamin K 2 analýza   analogy a deriváty   MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Japonsko MeSH

Předkládáme případ 5,5letého chlapce s těžkým globálním vývojovým opožděním, hypotonií, malým proporcionálním vzrůstem, neprospíváním, kraniofaciální dysmorfií a dalšími potížemi, u kterého se podařilo stanovit diagnózu pomocí celogenomového sekvenování (WGs). diagnostika byla realizována v rámci českého národního projektu BabyFox, který se zaměřuje na zhodnocení diagnostické a klinické využitelnosti rapidního celogenomového sekvenování (rapid trioWGs) u dětí hospitalizovaných na jednotkách intenzivní péče s podezřením na genetickou podstatu jejich potíží. u pacienta byla identifikována patogenní varianta v genu RNU4-2, která je od roku 2024 spojována s prevalentním onemocněním rnu4-2 syndromem neurovývojového opoždění, také známým pod názvem renu syndrom. ačkoli se jedná o nově popsané onemocnění, je renu syndrom jedním z nejrozšířenějších monogenních neurovývojových onemocnění, přičemž se odhaduje, že patogenní varianty v genu RNU4-2 jsou příčinou přibližně 0,4 % všech neurovývojových poruch. tento gen nekóduje protein, ale malou jadernou rna u4, díky čemuž jeho sekvence není stanovována při standardním celoexomovém sekvenování ani v rámci cílených sekvenačních panelů. Jeho význam tak zůstával až do roku 2024 přehlížen. případ renu syndromu zdůrazňuje význam celogenomového sekvenování pokrývajícího i nekódující části genomu v diagnostice vzácných genetických onemocnění a ukazuje, jak implementace moderních genomických metod může přispět k ukončení diagnostické odysey pacientů s dosud neobjasněnými neurovývojovými poruchami.

We present the case of a 5 and half year-old boy with severe global developmental delay, hypotonia, severe growth failure, failure to thrive, craniofacial dysmorphism, and other difficulties, who was diagnosed by whole genome sequencing (WGs). the diagnosis was carried out within the czech national project BabyFox. a pathogenic variant in the RNU4-2 gene was identified in the patient, which has been associated with the prevalent disorder known as rnu4-2 neurodevelopmental delay syndrome, also known as renu syndrome since 2024. although it is a newly described diseases, renu syndrome is one of the most prevalent monogenic neurodevelopmental disorder, with pathogenic variants in the rnu4-2 gene estimated to cause approximately 0.4% of all neurodevelopmental disorders. this gene does not encode a protein but rather a small nuclear rna u4, which means its sequence is not captured by standard whole-exome sequencing or targeted sequencing panels. as a result, its significance remained overlooked until 2024. the case of renu syndrome highlights the importance of whole-genome sequencing, which covers non-coding regions of the genome, in the diagnosis of rare genetic disorders. it also demonstrates how the implementation of modern genomic methods can help end the diagnostic odyssey for patients with previously unexplained neurodevelopmental disorders.

• Klíčová slova
• gen RNU4-2, ReNU syndrom,
• MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• mikrocefalie diagnóza   etiologie   genetika   MeSH
• neprospívání diagnóza   etiologie   MeSH
• neurovývojové poruchy * diagnóza   genetika   klasifikace   MeSH
• předškolní dítě MeSH
• RNA malá jaderná genetika   MeSH
• sekvenování celého genomu metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• kazuistiky MeSH

Euglenids have long been studied due to their unique physiology and versatile metabolism, providing underpinnings for much of our understanding of photosynthesis and biochemistry, and a growing opportunity in biotechnology. Until recently there has been a lack of genetic studies due to their large and complex genomes, but recently new technologies have begun to unveil their genetic capabilities. Whilst much research has focused on the model organism Euglena gracilis, other members of the euglenids have now started to receive due attention. Currently only poor nuclear genome assemblies of E. gracilis and Rhabdomonas costata are available, but there are many more plastid genome sequences and an increasing number of transcriptomes. As more assemblies become available, there are great opportunities to understand the fundamental biology of these organisms and to exploit them for biotechnology.

• MeSH
• Euglena gracilis genetika   MeSH
• Euglenida genetika   MeSH
• fylogeneze MeSH
• genom plastidový genetika   MeSH
• genom protozoální genetika   MeSH
• genomika * metody   MeSH
• transkriptom genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BackgroundOn 29 January 2024, the European Centre for Disease Prevention and Control distributed an alert about a metronidazole-resistant Clostridioides difficile outbreak of PCR ribotype (RT) 955 in England.AimWe aimed to investigate the presence of RT955 in Czech, Slovak and Polish C. difficile isolates and evaluate different culture media for detecting its metronidazole resistance.MethodsIsolates with binary toxin genes identified as 'unknown' by the WEBRIBO PCR ribotyping database up to 2023 were re-analysed after adding the RT955 profile to the database. The RT955 isolates were characterised by whole genome sequencing and tested for susceptibility to 15 antimicrobials.ResultsWe did not find RT955 in Czech (n = 6,661, 2012-2023) and Slovak (n = 776, 2015-2023) isolates, but identified 13 RT955 cases (n = 303, 2021-2023) in three hospitals in Poland. By whole genome multilocus sequence typing, 10 isolates clustered into one clonal complex including a sequence of United Kingdom strain ERR12670107, and shared similar antimicrobial resistance genes/mutations. All 13 isolates were resistant to ciprofloxacin/moxifloxacin, erythromycin/clindamycin and ceftazidime. All isolates had a mutation in the nimB gene promoter and in NimB (Tyr130Ser and Leu155Ile). The metronidazole resistance was detected in all isolates using brain-heart-infusion agar supplemented with haemin and Chocolate agar. Results were discrepant with the European Committee on Antimicrobial Susceptibility Testing-recommended Fastidious anaerobe agar and Brucella blood agar.ConclusionThe identification of clonally related haem-dependent metronidazole-resistant C. difficile RT955 in multiple hospitals indicates a need for prospective surveillance to estimate its prevalence in Europe.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální léková rezistence * genetika   MeSH
• Clostridioides difficile * genetika   účinky léků   izolace a purifikace   klasifikace   MeSH
• epidemický výskyt choroby MeSH
• klostridiové infekce * epidemiologie   mikrobiologie   farmakoterapie   MeSH
• lidé MeSH
• metronidazol * farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• multilokusová sekvenční typizace MeSH
• polymerázová řetězová reakce MeSH
• ribotypizace * MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Polsko MeSH
• Slovenská republika MeSH