Molecular Cytogenetics最新文献

{"title":"Clarification of the clinical significance of an intron variant in a case of Peutz-Jeghers syndrome with abnormal RNA splicing of STK11.","authors":"Aki Ishikawa, Masahiro Gotoh, Mineko Ushiama, Hiromi Sakamoto, Noriko Tanabe, Tomoko Watanabe, Hourin Cho, Masayoshi Yamada, Kokichi Sugano, Kouya Shiraishi, Makoto Hirata, Teruhiko Yoshida, Akihiro Sakurai","doi":"10.1186/s13039-025-00710-x","DOIUrl":"10.1186/s13039-025-00710-x","url":null,"abstract":"<p><p>Peutz–Jeghers syndrome is an autosomal dominant disease characterized by intestinal polyposis, mucocutaneous pigmentation, and an increased risk of various types of cancer. Germline mutations in STK11 (LKB1), which encodes serine/threonine kinase 11, have been identified as the major cause of Peutz–Jeghers syndrome. Here, we detected a rare variant of undetermined significance in intron 2 of STK11 using multi-gene panel analysis in a girl with clinically suspected Peutz–Jeghers syndrome. We confirmed this variant caused abnormal splicing in exons 2 and 3 using reverse transcription-PCR and Sanger sequencing. To validate the predicted impact of this variant on splicing, we performed functional analysis using a minigene assay. Functional analysis experiments demonstrated that this variant suppresses normal splicing, and the clinical significance of the STK11 variant, which was initially considered a variant of “uncertain significance,” was reclassified as “likely pathogenic” based on functional analysis. The interpretation of U12-type intronic variants remains particularly challenging due to limited data and the absence of specific recommendations in existing guidelines [1, 2], and when segregation analysis is difficult, functional analysis from splicing assays is essential to provide accurate genetic diagnosis and information for clinical management. However, further familial segregation analysis and further validation of potential exon-skipping events are necessary to fully characterize the splicing impact of this variant.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"20"},"PeriodicalIF":1.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883310","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":"Analysis of chromosomal aberrations in early pregnancy loss using high-throughput ligation-dependent probe amplification and single tandem repeats.","authors":"Rong Wei, Haili Hu, Shenlin Wang, Junxiang Tang, Jingran Li, Keting Tong, Chaohong Wang, Jiansheng Zhu","doi":"10.1186/s13039-025-00724-5","DOIUrl":"10.1186/s13039-025-00724-5","url":null,"abstract":"<p><strong>Introduction: </strong>Embryonic chromosomal abnormalities are the major cause of miscarriage. As a relatively novel genetic screening technology, high-throughput ligation-dependent probe amplification combined with short tandem repeat analysis (HLPA + STR) demonstrates significant clinical advantages, including shorter turnaround time, user-friendly technical workflows, and superior cost-effectiveness. The purpose of this study is to evaluate the frequency and characteristics of fetal chromosomal abnormalities using HLPA + STR in early pregnancy loss (EPL).</p><p><strong>Methods: </strong>A retrospective analysis was conducted on women who experienced EPL and underwent HLPA + STR. Group differences were compared using χ2 or Fisher's exact test, and multivariate logistic regression analysis was performed to examine the correlation between the fetal cytogenetic results and maternal age, gestational age, and history of miscarriage.</p><p><strong>Results: </strong>In total, 820 (61.75%) cases were detected to be chromosomal abnormalities, including 748 (91.22%) had numerical abnormalities, 59 (7.19%) had structural abnormalities, and 13 (1.59%) had chromosome mosaicism. The most frequent chromosomal abnormality was autosomal trisomy, of which trisomy (T) 16 was the most common, followed by sex chromosome monosomy and triploid. The incidence of fetal chromosomal abnormalities was significantly higher advanced maternal age (AMA) than in non-advanced maternal age (non-AMA) (p < 0.001). The AMA had a 1.93 times higher risk of fetal chromosomal abnormalities compared to the non-AMA (odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.39-2.68; p < 0.001). The risk of fetal chromosomal abnormalities in fetuses with a gestational age > 8 weeks was found to be 1.34 times higher compared to those with a gestational age ≤ 8 weeks (OR, 1.34; 95% CI, 1.07-1.69; p = 0.012). No statistically significant variation in fetal chromosomal abnormalities was observed in the history of miscarriage (p > 0.05).</p><p><strong>Conclusion: </strong>In conclusion, our results show that HLPA + STR is an effective strategy for cytogenetic analysis of EPL. In addition, Multivariate analysis identified advanced maternal age and gestational age are independent risk factors for fetal cytogenetic results in EPL, but not related to the history of miscarriage. Therefore, we recommend HLPA + STR as the first-tier screening tool for genetic evaluation in EPL. However, the results of complex abnormalities need to be combined with other techniques.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"19"},"PeriodicalIF":1.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847920","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 homozygous TRIP13 pathogenic variant associated with familiar oocyte arrest and prematurely condensed sperm chromosomes.","authors":"Michal Schweiger, André Reis, Esen Gümüslü, Alice Krebsova, Andreas Raab, Christine Lang, Denise Horn, Karl Sperling, Heidemarie Neitzel","doi":"10.1186/s13039-025-00722-7","DOIUrl":"10.1186/s13039-025-00722-7","url":null,"abstract":"<p><p>We report on a consanguineous family with two infertile sisters with oocyte arrest and prematurely condensed sperm chromosomes. A genome-wide linkage scan and exome sequencing revealed a homozygous variant in the gene for the thyroid receptor interacting protein 13 (TRIP13), c.518G˃A (p.Arg173Gln), affecting an evolutionary highly conserved amino acid within an ATP binding motif. Just recently, compound heterozygosity for this variant was described in a Chinese proband as pathogenic, confirming that the homozygous mutation is causative for the oocyte arrest. The TRIP13 gene and the orthologous yeast pch2 gene are, amongst others, involved in a meiotic checkpoint control. This checkpoint defect is obviously responsible for the premature condensation of the sperm chromosomes. TRIP13 and pch2 are involved in meiotic recombination. To exclude that it is involved in reciprocal somatic exchanges, we analyzed the rate of sister chromatid exchanges (SCEs) in the proband´s lymphoblastoid cells. Obviously, TRIP13 is not involved in this type of somatic recombination. Moreover, we tested whether TRIP13 can complement the defect of the yeast pch2 gene. Using a yeast deletion strain lacking pch2, we integrated plasmids containing either the yeast pch2 or the human TRIP13 gene, both harboring the wild-type or the mutant allele and assessed the crossingover rate between marker genes lys2 and leu2 as a measure of complementation. Evidence is presented that the human plasmids, unexpectedly also that with the mutation, could complement the pch2 deficient yeast strain, underlining that the evolutionary conservation at the molecular level obviously extends to the functional level.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"17"},"PeriodicalIF":1.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699112","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":"Comparative analysis of hybrid-SNP microarray and nanopore sequencing for detection of large-sized copy number variants in the human genome.","authors":"Catarina Silva, José Ferrão, Bárbara Marques, Sónia Pedro, Hildeberto Correia, Ana Valente, António Sebastião Rodrigues, Luís Vieira","doi":"10.1186/s13039-025-00721-8","DOIUrl":"10.1186/s13039-025-00721-8","url":null,"abstract":"<p><strong>Background: </strong>Nanopore sequencing is a technology that holds great promise for identifying all types of human genome variations, particularly structural variations. In this work, we used nanopore sequencing technology to sequence 2 human cell lines at low depth of coverage to call copy number variations (CNV), and compared the results variant by variant with chromosomal microarray (CMA) results.</p><p><strong>Results: </strong>We analysed sequencing data using CuteSV and Sniffles2 variant callers, compared breakpoints based on hybrid-SNP microarray, nanopore sequencing and Sanger sequencing, and analysed CNV coverage. From a total of 48 high confidence variants (truth set), variant calling detected 79% of the truth set variants, increasing to 86% for interstitial CNV. Simultaneous use of the 2 callers slightly increased variant calling. Both callers performed better when calling CNV losses than gains. Variant sizes from CMA and nanopore sequencing showed an excellent correlation, with breakpoints determined by nanopore sequencing differing by only 20 base pairs on average from Sanger sequencing. Nanopore sequencing also revealed that four variants concealed genomic inversions undetectable by CMA. In the 10 CNV not called in nanopore sequencing, 8 showed coverage evidence of genomic loss or gain, highlighting the need to improve SV calling algorithms performance.</p><p><strong>Conclusions: </strong>Nanopore sequencing offers advantages over CMA for structural variant detection, including the identification of multiple variant types and their breakpoints with increased precision. However, further improvements in variant calling algorithms are still needed for nanopore sequencing to become a highly robust and standardized approach for a comprehensive analysis of genomic structural variation.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"18"},"PeriodicalIF":1.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699113","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":"Assessing the reliability of ChatGPT in cytogenetic reporting and interpretation: implications for clinical use.","authors":"Alain Chebly, Lauren Veronese, Edith Chevret","doi":"10.1186/s13039-025-00717-4","DOIUrl":"10.1186/s13039-025-00717-4","url":null,"abstract":"<p><p>This study evaluates the accuracy of ChatGPT in generating chromosomal representations (formulas) based on ISCN rules in clinical cytogenetics. While ChatGPT generated correct answers for simple cases, it frequently failed in complex cases. These findings highlight the limitations of current AI tools in accurate clinical cytogenetic reporting, reinforcing the vital role of skilled clinical cytogeneticists for accurate interpretation and reporting.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"16"},"PeriodicalIF":1.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668054","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":"Cytogenetic finding of simultaneous inversion of chromosome 14 and tetrasomy 8 in a Pediatric B-Lymphoblastic Leukemia-a case report.","authors":"Kiran Sachwani, Rehab Pasha, Bushra Kaleem, Neelum Mansoor","doi":"10.1186/s13039-025-00715-6","DOIUrl":"10.1186/s13039-025-00715-6","url":null,"abstract":"<p><strong>Background: </strong>Clonal cytogenetic abnormalities in B-lymphoblastic leukemia (B-ALL) include structural and numerical chromosomal alterations, where numerical are the most common aberrations. Inversion 14 [inv(14)] is an infrequent finding in B-ALL, but its prognostic and therapeutic significance has not been previously explored.</p><p><strong>Case presentation: </strong>A 13-year-old boy diagnosed as B-ALL on bone marrow aspirate by flow cytometry is presented. Fluorescence in situ hybridization (FISH) for B-ALL panel was reported as normal. Nevertheless, his cytogenetic studies performed on bone marrow showed tetrasomy 8 and a pericentric inversion in chromosome 14.</p><p><strong>Conclusion: </strong>Inversion 14 is a rare finding in B-ALL, and its clinical relevance is worthy of further evaluation. The growing number of such cases reported emphasizes that there exists a possibility of a separate cytogenetic subset with diagnostic, prognostic or even therapeutic relevance.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"15"},"PeriodicalIF":1.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668055","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":"Mosaic tetrasomy 9p detected by CNV-seq but missed by traditional karyotyping in a prenatal case without dysmorphic features.","authors":"Xingkun Yang, Yasi Zhou, Xiaodan Zhu, Tingting Xiao, Miaoling Ou, Linghua Zhang, Xiang Huang, Xiaoling Guo, Chao Li","doi":"10.1186/s13039-025-00720-9","DOIUrl":"10.1186/s13039-025-00720-9","url":null,"abstract":"<p><strong>Introduction: </strong>A unique case of mosaic tetrasomy 9p was found using CNV-seq analysis of uncultured amniocytes, which was missed by karyotype analysis of cultured amniocytes.</p><p><strong>Case report: </strong>The karyotype was determined to be 46, XY, with mosaic duplication of chromosome 9 from p24.3 to p13.1 indicated by CNV sequencing in the initial amniocentesis. Subsequent prenatal testing revealed a normal karyotype, with FISH analysis of cultured amniocytes identifying 2% tetrasomy of chromosome 9p. The karyotype of cord blood revealed mosaic tetrasomy 9p, while CNV-seq on uncultured cord blood indicated nearly complete tetrasomy 9p.</p><p><strong>Conclusions: </strong>It is recommended to conduct CNV-seq or CMA on uncultured amniocytes in conjunction with karyotype analysis on cultured amniocytes. The presence of mosaic tetrasomy 9p during amniocentesis may result in either a benign condition or an adverse outcome, necessitating informed decision-making for pregnant women facing such circumstances.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"14"},"PeriodicalIF":1.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637637","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":"What the VAF? A guide to the interpretation of variant allele fraction, percent mosaicism, and copy number in cancer.","authors":"Adam C Smith, Hubert Tsui, Sila Usta, Jose-Mario Capo-Chichi","doi":"10.1186/s13039-025-00718-3","DOIUrl":"10.1186/s13039-025-00718-3","url":null,"abstract":"<p><p>The evolution of techniques used to identify structural variants (SVs) and copy number variants (CNVs) in genomes have seen significant development in the last decade. With the growing use of more technologies including chromosomal microarray, genome sequencing and genome mapping in clinical cytogenetics laboratories, reporting the frequency of SVs and CNVs has increased the complexity of genomic results. In conventional testing (e.g. karyotype or FISH) individual cells are analyzed and abnormalities are reported at the single cell level directly as a proportion of the analyzed cells. Whereas for bulk genome assays structural and sequence changes are often reported as variant allele frequencies and fractional copy number states. The International System of Cytogenomic Nomenclature (ISCN) recommends converting these values into a \"proportion of the sample\", which requires different calculations and underlying assumptions based on the data type. This review illustrates how the different methods of interpreting and reporting data are performed and identifies challenges in the conversion of these values to a proportion of the sample. We stress the need for careful interpretation of data with consideration for factors that may alter how proportions are reported including overlapping SVs and CNVs or regions with acquired homozygosity. We also demonstrate, using validation data of SVs and CNVs tested by multiple techniques how results are largely consistent across methodologies, but can show dramatic differences in rare circumstances. This review focuses on illustrating many of the challenges with aligning reporting using different techniques and their underlying assumptions. As hematologic disease classifications start to incorporate numeric limits (e.g. VAF defining thresholds), it is important for laboratory geneticists, pathologists and clinicians to appreciate the differences in methodologies, potential pitfalls and the nuances when comparing bulk genome analyses to the more conventional single cell techniques.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"13"},"PeriodicalIF":1.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591842","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":"Incorporating automation in a cytogenetics laboratory: three practitioners' perspectives on benefits and limitations.","authors":"Cecelia Miller, Jennie Thurston, Ninette Cohen","doi":"10.1186/s13039-025-00716-5","DOIUrl":"10.1186/s13039-025-00716-5","url":null,"abstract":"<p><p>Automation has been developed and continues to be refined for cytogenetics, including advances in the processing of samples, in analysis of conventional chromosome and fluorescence in situ hybridization (FISH) testing, and with artificial intelligence. Here we provide an overview of the various types of automation available to the cytogenetics laboratory and discuss possible benefits and limitations you may encounter based upon our collective experiences.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"12"},"PeriodicalIF":1.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285774","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":"Integrated cytogenetic and genomic profiling of the MDS-L cell line.","authors":"Julia Mestre, Lorea Chaparro-González, Isabel Granada, Mar Mallo, Emili Cid, Estefania Mancini, Oriol Calvete, Ruth M Risueño, Daniel T Starczynowski, Francesc Solé","doi":"10.1186/s13039-025-00714-7","DOIUrl":"10.1186/s13039-025-00714-7","url":null,"abstract":"<p><p>Among the human leukemia cell lines described in the literature, only the MDS-L cell line has been definitively established from a patient during the myelodysplastic syndrome (MDS) phase of the disease. However, the limited studies on its genomic complexity have restricted its applicability as an in vitro model for MDS. Here, we aimed to better characterize the chromosomal and genetic alterations of MDS-L. A comprehensive approach was employed combining conventional G banding, multicolor FISH (M-FISH), SNP arrays with the novel Optical Genome Mapping (OGM) technology. In addition, the mutational landscape was defined using targeted next-generation sequencing (NGS). G-banding revealed two karyotypically distinct cell populations, both exhibiting complex karyotypes. Using G-banding and OGM, we identified previously undescribed structural alterations, including der(1)t(1;7)(q11;q11.2), del(1)(q11), der(4)t(4;5)(p16;q11.2), i(5)(p10), der(6)t(6;15)(p21.3;q15), i(8)(q10), der(9)t(9;10)(q34;p11.21), der(19)t(6;19)(p13;p22) and i(22)(q10). Both OGM and SNP microarray analyses detected multiple copy number variants and regions of homozygosity. Chromosome breakpoints were precisely defined by OGM, allowing the identification of gene disruption events. Moreover, M-FISH technique validated the origins of additional chromosomal material observed in the karyotype, identified cryptic rearrangements, and distinguished the two clonal populations within the cell line. Finally, NGS revealed mutations in CEBPA, NRAS, TET2 and TP53 genes associated with MDS pathology. This multi-technique approach has enabled a precise characterization of the MDS-L cell line's genomic complexity, highlighting the unique contributions of each technique in uncovering various genetic alterations and establishing a valuable resource for mechanistic studies and pre-clinical drug development.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"11"},"PeriodicalIF":1.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275407","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}