Cytogenetic and Genome Research最新文献

{"title":"A Heterozygous Variant of FGF13 Caused X-Linked Developmental and Epileptic Encephalopathy 90 in a Chinese Family.","authors":"Haiying Cheng, Pu Miao, Ye Wang, Yufan Guo, Liuyan Gao, Yuting Lou, Fan Yang, Mengmeng Liang, Jianhua Feng","doi":"10.1159/000531932","DOIUrl":"10.1159/000531932","url":null,"abstract":"<p><p>Developmental and epileptic encephalopathy (DEE) refers to a group of severe epilepsy encephalopathy and development disorders, and its typical clinical features include seizures, drug resistance, and developmental delay or regression. To date, limited studies have reported DEEs driven by FGF13. Here, we reported a girl with developmental and epileptic encephalopathy 90 caused by variant of FGF13. Her electroencephalogram (EEG) showed discontinuous hypsarrhythmia, and a heterozygous nonsynonymous variant in FGF13 [NM_004114.4: c.5C&gt;G, p.(Ala2Gly)] was identified from the proband. The variant was not reported in public databases such as gnomAD and Exome Aggregation Consortium (ExAC), and was predicted to be damaging to proteins and classified as likely pathogenic according to the ACMG guidelines. The seizure was finally controlled by a combination of ACTH + zonisamide (10 mg/kg.d) + levetiracetam (52 mg/kg.d) + clonazepam (0.7 mg/kg.d).</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous EYFP-CENH3/H2B-DsRed Expression Is Impaired Differentially in Meristematic and Differentiated Nuclei of Arabidopsis Double Transformants.","authors":"Veit Schubert, Andrea Weißleder, Inna Lermontova","doi":"10.1159/000533317","DOIUrl":"10.1159/000533317","url":null,"abstract":"<p><p>Fluorescence live-cell microscopy is important in cell biology to perform artifact-free investigations. To analyze the dynamics of chromatin and centromeres at different stages of the cell cycle in nuclei and chromosomes, we performed simultaneous EYFP-CENH3/H2B-DsRed and single H2B-YFP transformations in Arabidopsis wild-type and cohesin T-DNA mutants. All constructs were under the control of the strong CaMV 35S promoter. While a strong silencing of fluorescence expression occurred differently in leaf and root tissues in the double transformants, nearly all single-transformed wild-type and most mutant cells showed H2B-YFP fluorescence. It seems that for an efficient co-expression of two fluorescence proteins, endogenous promoters and terminators should be used.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Micronuclei Frequency in the Peripheral Blood of Adult and Pediatric Patients Receiving Fractionated Total Body Irradiation.","authors":"Karthik Kanagaraj, Michelle A Phillippi, Pratyush Narayan, Barbara Szolc, Jay R Perrier, Amanda McLane, Suzanne L Wolden, Christopher A Barker, Qi Wang, Sally A Amundson, David J Brenner, Helen C Turner","doi":"10.1159/000534433","DOIUrl":"10.1159/000534433","url":null,"abstract":"<p><p>The cytokinesis-block micronucleus (CBMN) assay is an established method for assessing chromosome damage in human peripheral blood lymphocytes resulting from exposure to genotoxic agents such as ionizing radiation. The objective of this study was to measure cytogenetic DNA damage and hematology parameters in vivo based on MN frequency in peripheral blood lymphocytes (PBLs) from adult and pediatric leukemia patients undergoing hematopoietic stem cell transplantation preceded by total body irradiation (TBI) as part of the conditioning regimen. CBMN assay cultures were prepared from fresh blood samples collected before and at 4 and 24 h after the start of TBI, corresponding to doses of 1.25 Gy and 3.75 Gy, respectively. For both age groups, there was a significant increase in MN yields with increasing dose (p &lt; 0.05) and dose-dependent decrease in the nuclear division index (NDI; p &lt; 0.0001). In the pre-radiotherapy samples, there was a significantly higher NDI measured in the pediatric cohort compared to the adult due to an increase in the percentage of tri- and quadri-nucleated cells scored. Complete blood counts with differential recorded before and after TBI at the 24-h time point showed a rapid increase in neutrophil (p = 0.0001) and decrease in lymphocyte (p = 0.0006) counts, resulting in a highly elevated neutrophil-to-lymphocyte ratio (NLR) of 14.45 ± 1.85 after 3.75 Gy TBI (pre-exposure = 4.62 ± 0.49), indicating a strong systemic inflammatory response. Correlation of the hematological cell subset counts with cytogenetic damage, indicated that only the lymphocyte subset survival fraction (after TBI compared with before TBI) showed a negative correlation with increasing MN frequency from 0 to 1.25 Gy (r = -0.931; p = 0.007). Further, the data presented here indicate that the combination of CBMN assay endpoints (MN frequency and NDI values) and hematology parameters could be used to assess cytogenetic damage and early hematopoietic injury in the peripheral blood of leukemia patients, 24 h after TBI exposure.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Partial Deletion of the TBL1XR1 Gene Detected Using SNP Array in a Patient with Motor Delay, Growth Failure, and Klinefelter Syndrome.","authors":"Elena García-Payá, Paula Sirera Sirera, Isabel Huertas-García, Sofía Daniela Hernández Romero, Julia Olivas García","doi":"10.1159/000534530","DOIUrl":"10.1159/000534530","url":null,"abstract":"<p><strong>Introduction: </strong>Co-existence pathogenic copy number variation with aneuploidy is a rare phenomenon. Whole TBL1XR1 gene deletions are described and associated with autosomal dominant intellectual development disorder-41 (#616944). However, the phenotypical expression of the TBL1XR1 partial deletion is poorly described.</p><p><strong>Case presentation: </strong>We describe the case of a male, aged 18 months, who presented delayed motor development, gait disturbance, mild generalized hypotonia, minor dysmorphic features, and growth failure, in addition to Klinefelter syndrome (KS). The single nucleotide polymorphism array revealed the de novo pathogenic interstitial deletion of chromosome 3q26.32 of 202 kb size that encompassed the first two exons of one relevant coding gene: TBL1XR1 (*608,628).</p><p><strong>Conclusion: </strong>We report a male without clinical signs of KS and overlapped phenotypical features with another TBL1XR1-related disease: Pierpont syndrome (#602342). This patient extends the phenotypic spectrum of TBL1XR1 gene pathogenic variants.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden Y Chromosome Material and Congenital Cardiovascular Malformations in a Cohort of Turner Syndrome Patients with 45,X Blood Karyotype.","authors":"Emediong Q Udo, Tate Truly, Andrew Peters, Siddharth K Prakash, Michelle Rivera, David Felipe Rodriguez-Buritica","doi":"10.1159/000535771","DOIUrl":"10.1159/000535771","url":null,"abstract":"<p><strong>Introduction: </strong>Bicuspid aortic valve is the most common congenital cardiac malformation (CCM) in adults and is 30-50 times more frequent in Turner syndrome (TS). We hypothesize that both X and Y chromosome dosages contribute to the prevalence of CCM in TS. The recognition of genotype-phenotype correlations may improve risk stratification of patients with 45,X karyotypes who have cryptic Y chromosome mosaicism.</p><p><strong>Methods: </strong>Utilizing data and samples from the UTHealth Turner Syndrome Research Registry, we correlated Y chromosome DNA identified by multiplex quantitative PCR and SNP microarrays with the presence of congenital heart lesions.</p><p><strong>Results: </strong>We identified Y chromosome DNA in more than 10% of registry participants, including 2 participants who had no detectable Y DNA by karyotype or SNP microarray.</p><p><strong>Conclusions: </strong>There were no significant correlations between the presence of Y DNA and CCM.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xp22.33p22.13 Duplication in a Male Patient Carrying a Recombinant X Chromosome Derived from an Inherited Intrachromosomal Insertion.","authors":"Tatiana Mozer Joaquim, Scott David Roy, Clarissa Gondim Picanço de Albuquerque, Carlos Henrique Paiva Grangeiro, Jeremy A Squire, Maisa Yoshimoto, Lucia Martelli","doi":"10.1159/000532051","DOIUrl":"10.1159/000532051","url":null,"abstract":"<p><p>Intrachromosomal insertions are complex structural rearrangements that are challenging to interpret using classical cytogenetic methods. We report a male patient carrying a recombinant X chromosome derived from a maternally inherited intrachromosomal insertion. The patient exhibited developmental delay, intellectual disability, behavioral disorder, and dysmorphic facial features. To accurately identify the rearrangements in the abnormal X chromosome, additional cytogenetic studies were conducted, including fluorescence in situ hybridization (FISH), multicolor-banding FISH, and array comparative genomic hybridization. The results showed a recombinant X chromosome, resulting in a 13.05 Mb interstitial duplication of segment Xp22.33-Xp22.13, which was inserted at cytoband Xq26.1. The duplicated region encompasses 99 genes, some of which are associated with the patient's clinical manifestations. We propose that the combined effects of the Xp-duplicated genes may contribute to the patient's phenotype.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10215761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tandem Triplication 11p15.5-ICR1 (H19/IGF2) Detected by Microarray and Optical Genome Mapping in a Prenatal Beckwith-Wiedemann Case.","authors":"Elisabet Lloveras, Cristina Pérez, Begoña Mendez, Susana Martin, Claudia Alves, Margarida Reis-Lima","doi":"10.1159/000531703","DOIUrl":"10.1159/000531703","url":null,"abstract":"<p><p>Optical genome mapping (OGM) appears as a new tool for matching standard cytogenetic methods (karyotype and microarray) into a single assay. The chromosomal region 11p15.5 harbours two differentially methylated regions, the imprinting centre regions 1 and 2 (ICR1, ICR2). Disturbances in both regions alter human growth and are associated with two imprinting disorders, Beckwith-Wiedemann (BWS) and Silver-Russell syndromes. Herein, we present a prenatal case with a triplication in 11p15.5, including the H19/IGF2 imprinted region, detected by microarray and OGM. A 30-year-old pregnant woman of 17 weeks of gestation was referred for prenatal karyotype and microarray study because of increased nuchal translucency, short femur, megabladder, hyperechogenic bowel, and renal ectasia. Microarray, OGM, and MS-MLPA were performed, and a tandem cis-triplication in 11p15.5 and hypermethylation of the ICR1 region, compatible with BWS was detected. OGM, with its power to detect all classes of structural variants, including copy number variants, at a higher resolution than traditional cytogenetic methods can play a significant role in prenatal care and management as a next-generation cytogenomic tool. This study further supports the hypotheses that the amplification/duplication-triplication of the H19/IGF2 region could be related to BWS if it is of paternal origin.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paper-Based Vertical Flow Immunoassay for the Point-of-Care Multiplex Detection of Radiation Dosimetry Genes.","authors":"Jerome Lacombe, Alexander J Summers, Ashkan Khanishayan, Yasaman Khorsandian, Isabella Hacey, Wyatt Blackson, Frederic Zenhausern","doi":"10.1159/000531702","DOIUrl":"10.1159/000531702","url":null,"abstract":"<p><p>In a nuclear or radiological incident, first responders must quickly and accurately measure radiation exposure among civilians as medical countermeasures are radiation dose-dependent and time-sensitive. Although several approaches have been explored to measure absorbed radiation dose, there is an important need to develop point-of-care (POC) bioassay devices that can be used immediately to triage thousands of individuals potentially exposed to radiation. Here we present a proof-of-concept study showing the use of a paper-based vertical flow immunoassay (VFI) to detect radiation dosimetry genes. Using labeled primers during amplification and a multiplex membrane, our results showed that the nucleic acid VFI can simultaneously detect two biodosimetry genes, CDKN1A and DDB2, as well as one housekeeping gene MRPS5. The assay demonstrated good linearity and precision with an inter- and intra-assay coefficient of variance &lt;20% and &lt;10%, respectively. Moreover, the assay showed its ability to discriminate non-irradiated controls (0 Gy) from irradiated samples (1 + 2 Gy) with an overall sensitivity of 62.5% and specificity of 100% (AUC = 0.8672, 95% CI: 0.723-1.000; p = 0.004). Interestingly, the gene combination also showed a dose-dependent response for 0, 1, and 2 Gy, similar to data obtained by real-time PCR benchmark. These preliminary results suggest that a VFI platform can be used to detect simultaneously multiple genes that can be then quantified, thus offering a new approach for a POC biodosimetry assay that could be rapidly deployed on-site to test a large population and help triage and medical management after radiological event.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9695919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supernumerary B Chromosomes of Tetragonisca fiebrigi Share Repeat Content with Standard Chromosome Set of both T. fiebrigi and Tetragonisca angustula (Apidae: Meliponini).","authors":"Marina Souza Cunha, Camila Moura Novaes, Jaqueline Amorim Pereira, Martinha Mapingala Capoco, Tânia Maria Fernandes-Salomão, Denilce Meneses Lopes","doi":"10.1159/000533431","DOIUrl":"10.1159/000533431","url":null,"abstract":"<p><p>The stingless bees Tetragonisca angustula and Tetragonisca fiebrigi are widely distributed in Brazil, and both are commonly known as \"jataí.\" Our goal was to investigate the possible origin of the B chromosomes in T. fiebrigi, a cytotaxonomic trait that differentiates T. fiebrigi from T. angustula. We analyzed diploid chromosome number (2n), B chromosome incidence, patterns of constitutive heterochromatin, and in situ localization of different repetitive DNA probes in T. angustula and T. fiebrigi. Both species displayed 2n = 34, with similar karyotype structures. One to three B chromosomes were observed in T. fiebrigi only. Constitutive heterochromatin was distributed on one arm of all chromosomes in both species, and T. fiebrigi B chromosomes were mainly heterochromatic with one euchromatic extremity. The (GA)15 and (CAA)10 microsatellite probes marked the euchromatic arms of all chromosomes in both species without marking the B chromosomes. The 18S ribosomal DNA (rDNA) probe marked 10 chromosomes in T. angustula and 6 A chromosomes in T. fiebrigi with an additional marking on 1B in individuals with 3B. The Tan-Bsp68I repetitive DNA probe marked the heterochromatic portion of all T. fiebrigi A and B chromosomes. This probe also marked the heterochromatic portion of all T. angustula chromosomes; therefore, both alternative hypotheses to the B chromosome origin are possible: (i) from the A chromosome complement of T. fiebrigi (intraspecific origin); or (ii) a by-product of genome reshuffling following the hybridization between T. fiebrigi and T. angustula (interspecific origin).</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9946580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Mutations in Refractory/Relapsed Diffuse Large B-Cell Lymphoma by Targeted Gene Sequencing.","authors":"Aditi Sharma, Ashim Das, Amanjit Bal, Radhika Srinivasan, Pankaj Malhotra, Gaurav Prakash, Rajender Kumar","doi":"10.1159/000535400","DOIUrl":"10.1159/000535400","url":null,"abstract":"<p><strong>Introduction: </strong>Whole-genome sequencing of diffuse large B-cell lymphoma (DLBCL) has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness.</p><p><strong>Material and methods: </strong>A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and 8 cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse.</p><p><strong>Results: </strong>A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort.</p><p><strong>Discussion: </strong>The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}