Molecular Cytogenetics最新文献

{"title":"Comprehensive analysis of three female patients with different types of X/Y translocations and literature review.","authors":"Shanquan Liu,&nbsp;Jiemei Zheng,&nbsp;Xijing Liu,&nbsp;Yi Lai,&nbsp;Xuan Zhang,&nbsp;Tiantian He,&nbsp;Yan Yang,&nbsp;He Wang,&nbsp;Xuemei Zhang","doi":"10.1186/s13039-023-00639-z","DOIUrl":"https://doi.org/10.1186/s13039-023-00639-z","url":null,"abstract":"<p><strong>Background: </strong>X/Y translocations are highly heterogeneity in terms of clinical genetic effects, and most patients lack complete pedigree analysis for clinical and genetic characterization.</p><p><strong>Results: </strong>This study comprehensively analyzed the clinical and genetic characteristics of three new patients with X/Y translocations. Furthermore, cases with X/Y translocations reported in the literature and studies exploring the clinical genetic effects in patients with X/Y translocations were reviewed. All three female patients were carriers of X/Y translocations with different phenotypes. The karyotype for patient 1 was 46,X,der(X)t(X;Y)(p22.33;q12)mat, patient 2 was 46,X,der(X)t(X;Y)(q21.2;q11.2)dn, and patient 3 was 46,X,der(X)t(X;Y)(q28;q11.223)t(Y;Y)(q12;q11.223)mat. C-banding analysis of all three patients revealed a large heterochromatin region in the terminal region of the X chromosome. All patients underwent chromosomal microarray analysis, which revealed the precise copy number loss or gain. Data on 128 patients with X/Y translocations were retrieved from 81 studies; the phenotype of these patients was related to the breakpoint of the chromosome, size of the deleted region, and their sex. We reclassified the X/Y translocations into new types based on the breakpoints of the X and Y chromosomes.</p><p><strong>Conclusion: </strong>X/Y translocations have substantial phenotypic diversity, and the genetic classification standards are not unified. With the development of molecular cytogenetics, it is necessary to combine multiple genetic methods to obtain an accurate and reasonable classification. Thus, clarifying their genetic causes and effects promptly will help in genetic counseling, prenatal diagnosis, preimplantation genetic testing, and improvement in clinical treatment strategies.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"7"},"PeriodicalIF":1.3,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9495393","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":"Population monitoring of trisomy 21: problems and approaches.","authors":"Karl Sperling,&nbsp;Hagen Scherb,&nbsp;Heidemarie Neitzel","doi":"10.1186/s13039-023-00637-1","DOIUrl":"https://doi.org/10.1186/s13039-023-00637-1","url":null,"abstract":"<p><p>Trisomy 21 (Down syndrome) is the most common autosomal aneuploidy among newborns. About 90% result from meiotic nondisjunction during oogenesis, which occurs around conception, when also the most profound epigenetic modifications take place. Thus, maternal meiosis is an error prone process with an extreme sensitivity to endogenous factors, as exemplified by maternal age. This contrasts with the missing acceptance of causal exogenous factors. The proof of an environmental agent is a great challenge, both with respect to ascertainment bias, determination of time and dosage of exposure, as well as registration of the relevant individual health data affecting the birth prevalence. Based on a few exemplary epidemiological studies the feasibility of trisomy 21 monitoring is illustrated. In the nearer future the methodical premises will be clearly improved, both due to the establishment of electronic health registers and to the introduction of non-invasive prenatal tests. Down syndrome is a sentinel phenotype, presumably also with regard to other congenital anomalies. Thus, monitoring of trisomy 21 offers new chances for risk avoidance and preventive measures, but also for basic research concerning identification of relevant genomic variants involved in chromosomal nondisjunction.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"6"},"PeriodicalIF":1.3,"publicationDate":"2023-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9529382","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":"Identification of complex and cryptic chromosomal rearrangements by optical genome mapping.","authors":"Shanshan Shi,&nbsp;Peizhi Huang,&nbsp;Ruiling Yan,&nbsp;Ruiman Li","doi":"10.1186/s13039-023-00636-2","DOIUrl":"https://doi.org/10.1186/s13039-023-00636-2","url":null,"abstract":"<p><strong>Background: </strong>Optical genome mapping (OGM) has developed into a highly promising method for detecting structural variants (SVs) in human genomes. Complex chromosomal rearrangements (CCRs) and cryptic translocations are rare events that are considered difficult to detect by routine cytogenetic methods. In this study, OGM was applied to delineate the precise chromosomal rearrangements in three cases with uncertain or unconfirmed CCRs detected by conventional karyotyping and one case with a cryptic translocation suggested by fetal chromosomal microarray analysis (CMA).</p><p><strong>Results: </strong>In the three cases with CCRs, OGM not only confirmed or revised the original karyotyping results but also refined the precise chromosomal structures. In the case with a suspected translocation not detected by karyotyping, OGM efficiently identified the cryptic translocation and defined the genomic breakpoints with relatively high accuracy.</p><p><strong>Conclusions: </strong>Our study confirmed OGM as a robust alternative approach to karyotyping for the detection of chromosomal structural rearrangements, including CCRs and cryptic translocations.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"5"},"PeriodicalIF":1.3,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9729533","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":"Prenatal diagnosis of ultrasound soft markers in a single medical center of mainland China.","authors":"Yanhong Zhou,&nbsp;Siqi Wu,&nbsp;Jin Han,&nbsp;Li Zhen,&nbsp;Xin Yang,&nbsp;Ru Li,&nbsp;Yongling Zhang,&nbsp;Xiangyi Jing,&nbsp;Fucheng Li,&nbsp;Huishu Liu","doi":"10.1186/s13039-022-00633-x","DOIUrl":"https://doi.org/10.1186/s13039-022-00633-x","url":null,"abstract":"<p><strong>Background: </strong>There are a few studies on the chromosomal aberration of Ultrasound soft markers (USMs). The aim of this study was to determine the detection rate of clinically significant chromosomal abnormalities (CSCA) in fetuses with different USMs.</p><p><strong>Methods: </strong>This study included fetuses with USMs who underwent invasive prenatal diagnosis for karyotype and/or chromosomal microarray (CMA) by categorizing into two groups: a single USM (SUSM) and multiple USMs (MUSMs).</p><p><strong>Results: </strong>Of the 358 cases with USMs, CSCA occurred in 3.09% (8/259) and 8.08% (8/99) of the SUSM and MUSM groups, respectively (P < 0.05). Of 16 cases identified with CSCA, theoretically 68.75% (11/16) could be detected by karyotype, while 31.25% (5/16) could be recognized only by CMA. Among CSCA cases, the most frequent USM was an absent or hypoplastic nasal bone (62.5%, 10/16). In cases with negative karyotypes and/or CMA, follow-up results were available in 307 cases, including 292 term deliveries, 6 preterm deliveries, 8 terminations of pregnancy due to USMs, and 1 still birth.</p><p><strong>Conclusion: </strong>MUSMs increased the risk of chromosomal abnormalities. An absent or hypoplastic nasal bone was the most clinically significant marker either alone or in combination with other USMs. Most of SUSM had a good prognosis.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"3"},"PeriodicalIF":1.3,"publicationDate":"2023-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10683413","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 culture failure and its causes in hematological disorders; a single centre perspective.","authors":"Sarah Javed, Jawad Hassan, Maliha Naz, Saira Shan, Madiha Abid, Tahir Sultan Shamsi","doi":"10.1186/s13039-022-00635-9","DOIUrl":"10.1186/s13039-022-00635-9","url":null,"abstract":"<p><strong>Objective: </strong>To highlight the reasons of culture failure in bone marrow aspirate samples sent for Cytogenetic analysis and to identify the associated parameters causing this impact.</p><p><strong>Methodology: </strong>This is a retrospective cross-sectional study conducted in the Clinical and Molecular Cytogenetics Laboratory of NIBD Hospital, Karachi, Pakistan. The rates of culture failure are assessed from the year 2017-2020 along with their reasons. Bone Marrow aspirate samples of patients with hematological malignancies were cultured for chromosomal analysis, both at the time of diagnosis or relapse. Statistical analysis was performed using SPSS version 25.</p><p><strong>Results: </strong>A total of 1061 bone marrow aspirate samples were assessed for cytogenetic culture failures from the duration of 2017 to 2020. Ratio of males was predominantly higher i.e. 62.7% than female 37.3% with Mean ± SD age was 36.78 ± 18.94. Frequency of culture failure in the year 2020 was relatively high 20% as compared to the preceding years i.e. 8% in 2017, 6% in 2018, 7% in 2019. However, the patients were diagnosed with the following hematological malignancies; ALL 23%, CML 17.1%, AML 16.5% and AA 12.5%. Among the reasons of culture failure, cytogenetic analysis of patients with on-going chemo resulted in significant culture failures with p-value < 0.001 and the hematological malignancy, Acute Promyelocytic Leukemia, significantly impacted the growth of bone marrow aspirate cultures, with p-value < 0.001.</p><p><strong>Conclusion: </strong>Significant findings were associated with causative factors of culture failure including on-going treatment and sample issues of clotted bone marrow as well as with the clinical diagnosis. These evaluations facilitated in overcoming the rise in culture failures. As per our knowledge, no such data, discussing the effects of various parameters such as sample quality, diagnosis, effects of treatment etc., has been documented previously.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"4"},"PeriodicalIF":1.3,"publicationDate":"2023-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10692620","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":"Frequent copy number variants in a cohort of Mexican-Mestizo individuals.","authors":"Silvia Sánchez, Ulises Juárez, Julieta Domínguez, Bertha Molina, Rehotbevely Barrientos, Angélica Martínez-Hernández, Alessandra Carnevale, Patricia Grether-González, Dora Gilda Mayen, Camilo Villarroel, Esther Lieberman, Emiy Yokoyama, Victoria Del Castillo, Leda Torres, Sara Frias","doi":"10.1186/s13039-022-00631-z","DOIUrl":"10.1186/s13039-022-00631-z","url":null,"abstract":"<p><strong>Background: </strong>The human genome presents variation at distinct levels, copy number variants (CNVs) are DNA segments of variable lengths that range from several base pairs to megabases and are present at a variable number of copies in human genomes. Common CNVs have no apparent influence on the phenotype; however, some rare CNVs have been associated with phenotypic traits, depending on their size and gene content. CNVs are detected by microarrays of different densities and are generally visualized, and their frequencies analysed using the HapMap as default reference population. Nevertheless, this default reference is inadequate when the samples analysed are from people from Mexico, since population with a Hispanic genetic background are minimally represented. In this work, we describe the variation in the frequencies of four common CNVs in Mexican-Mestizo individuals.</p><p><strong>Results: </strong>In a cohort of 147 unrelated Mexican-Mestizo individuals, we found that the common CNVs 2p11.2 (99.6%), 8p11.22 (54.5%), 14q32.33 (100%), and 15q11.2 (71.1%) appeared with unexpectedly high frequencies when contrasted with the HapMap reference (ChAS). Yet, while when comparing to an ethnically related reference population, these differences were significantly reduced or even disappeared.</p><p><strong>Conclusion: </strong>The findings in this work contribute to (1) a better description of the CNVs characteristics of the Mexican Mestizo population and enhance the knowledge of genome variation in different ethnic groups. (2) emphasize the importance of contrasting CNVs identified in studied individuals against a reference group that-as best as possible-share the same ethnicity while keeping this relevant information in mind when conducting CNV studies at the population or clinical level.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"2"},"PeriodicalIF":1.3,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10519020","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":"Cytogenomic epileptology.","authors":"Ivan Y Iourov,&nbsp;Alexandr P Gerasimov,&nbsp;Maria A Zelenova,&nbsp;Natalya E Ivanova,&nbsp;Oksana S Kurinnaia,&nbsp;Yulia M Zabrodskaya,&nbsp;Irina A Demidova,&nbsp;Evgeny R Barantsevich,&nbsp;Kirill S Vasin,&nbsp;Alexey D Kolotii,&nbsp;Vseslav V Ushanov,&nbsp;Darya A Sitovskaya,&nbsp;Timur B-A Lobzhanidze,&nbsp;Maria E Iuditskaia,&nbsp;Nikita S Iakushev,&nbsp;Muslim M Zhumatov,&nbsp;Svetlana G Vorsanova,&nbsp;Konstantin A Samochernyh","doi":"10.1186/s13039-022-00634-w","DOIUrl":"https://doi.org/10.1186/s13039-022-00634-w","url":null,"abstract":"<p><p>Molecular cytogenetic and cytogenomic studies have made a contribution to genetics of epilepsy. However, current genomic research of this devastative condition is generally focused on the molecular genetic aspects (i.e. gene hunting, detecting mutations in known epilepsy-associated genes, searching monogenic causes of epilepsy). Nonetheless, chromosomal abnormalities and copy number variants (CNVs) represent an important part of genetic defects causing epilepsy. Moreover, somatic chromosomal mosaicism and genome/chromosome instability seem to be a possible mechanism for a wide spectrum of epileptic conditions. This idea becomes even more attracting taking into account the potential of molecular neurocytogenetic (neurocytogenomic) studies of the epileptic brain. Unfortunately, analyses of chromosome numbers and structure in the affected brain or epileptogenic brain foci are rarely performed. Therefore, one may conclude that cytogenomic area of genomic epileptology is poorly researched. Accordingly, molecular cytogenetic and cytogenomic studies of the clinical cohorts and molecular neurocytogenetic analyses of the epileptic brain appear to be required. Here, we have performed a theoretical analysis to define the targets of the aforementioned studies and to highlight future directions for molecular cytogenetic and cytogenomic research of epileptic disorders in the widest sense. To succeed, we have formed a consortium, which is planned to perform at least a part of suggested research. Taking into account the nature of the communication, \"cytogenomic epileptology\" has been introduced to cover the research efforts in this field of medical genomics and epileptology. Additionally, initial results of studying cytogenomic variations in the Russian neurodevelopmental cohort are reviewed with special attention to epilepsy. In total, we have concluded that (i) epilepsy-associated cytogenomic variations require more profound research; (ii) ontological analyses of epilepsy genes affected by chromosomal rearrangements and/or CNVs with unraveling pathways implicating epilepsy-associated genes are beneficial for epileptology; (iii) molecular neurocytogenetic (neurocytogenomic) analysis of postoperative samples are warranted in patients suffering from epileptic disorders.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"1"},"PeriodicalIF":1.3,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501085","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":"Prenatal diagnosis and molecular cytogenetic analyses of a paternal inherited deletion of 1q23.3 encompassing PBX1 gene.","authors":"Man Luo, Xia Gu, Ting Zhou, Chaoli Chen","doi":"10.1186/s13039-022-00632-y","DOIUrl":"10.1186/s13039-022-00632-y","url":null,"abstract":"<p><strong>Background: </strong>Patients with deletions involving the long arm of chromosome 1 are rare. The PBX1 gene is located on chromosome 1q23.3. PBX1 encodes a transcription factor which promotes protein-protein interaction and plays a crucial role in several developmental processes. PBX1 haploinsufficiency had been reported to lead syndromic congenital anomalies of kidney and urinary tract (CAKUT) in humans.</p><p><strong>Case presentation: </strong>In this research, a 24-year-old woman (gravida 1, para 0) underwent amniocentesis at 22 weeks' gestation because of a horseshoe kidney of the fetus on prenatal ultrasound.</p><p><strong>Results: </strong>Chromosomal microarray analysis (CMA) from this family revealed a 1.14 Mb paternal inherited deletion on chromosome 1q23.3, spanning from position 163,620,000 to 164,760,000 (hg19). Trio whole-exome sequencing (WES) showed heterozygous deletions in exons 1-2 of the PBX1 in fetal and paternal samples. At the 3-year follow-up, the baby did not have an abnormal phenotype except a horseshoe kidney.</p><p><strong>Conclusion: </strong>We provide a detailed description of the phenotype in a family with paternal inherited deletion of 1q23.3 encompassing exons 1-2 of the PBX1 gene. Combination of karyotype analysis, CMA, WES, prenatal ultrasound and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"15 1","pages":"53"},"PeriodicalIF":1.3,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10788447","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":"Molecular cytogenetic and phenotypic characterization of Phelan McDermid and 22q13 duplication syndrome: a case report.","authors":"Yousif Khalifa,&nbsp;Hisham Y Hassan,&nbsp;Anja Weise,&nbsp;Thomas Liehr,&nbsp;Haya Alkhayyat","doi":"10.1186/s13039-022-00629-7","DOIUrl":"https://doi.org/10.1186/s13039-022-00629-7","url":null,"abstract":"<p><strong>Background: </strong>Phelan-McDermid syndrome (PHMDS) is a rare genetic disorder mostly caused by haploinsufficincy of SHANK3 gene, and characterized by neonatal hypotonia, developmental delay, minor dysmorphic features, seizures and behavior problems. Literature of this syndrome is scanty and confusing, and represents a challenge for pediatricians, in terms of finding the correct diagnoses.</p><p><strong>Case presentation: </strong>In a postnatal case with hypotonia and dysmorphic features a de novo ring chromosome r(22) leading to in parallel microdeletion and micro duplication in 22q13 was diagnosed by banding cytogenetics, and further characterized in detail by molecular cytogenetic and chromosomal microarray.</p><p><strong>Conclusion: </strong>Here a rare PHMDS case caused by a r(22) is presented. Less than 10 comparable cases are reported in the literature. The present case highlights the importance of conducting genetic counseling and appropriate genetic tests for newborns with mild dysmorphic features.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"15 1","pages":"52"},"PeriodicalIF":1.3,"publicationDate":"2022-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399453","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 treatment-refractory aggressive MDS-MLD with multiple highly complex chromosome 5 intrachromosomal rearrangements: a case report.","authors":"Ramakrishnan Sasi,&nbsp;Jamie Senft,&nbsp;Michelle Spruill,&nbsp;Subit Barua,&nbsp;Sam Dougaparsad,&nbsp;Jeffrey A Vos,&nbsp;Peter L Perrotta","doi":"10.1186/s13039-022-00630-0","DOIUrl":"https://doi.org/10.1186/s13039-022-00630-0","url":null,"abstract":"<p><strong>Background: </strong>A patient with a myelodysplastic neoplasm exhibited a karyotype with multiple complex chromosome 5 rearrangements. This patient appeared to have a catastrophic cytogenetic event that manifested as a treatment-refractory aggressive form of disease, which lead to patient demise within one year. Both the clinical presentation and disease course were unusual based on the medical history and morphologic findings. Such cases of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD) with complex abnormalities are not reported in the literature.</p><p><strong>Case presentation: </strong>The patient was a 62-year-old female who presented with pancytopenia and dyspnea. The morphologic appearance of the peripheral blood smear and bone marrow biopsy, along with flow cytometric findings, favored the diagnosis of MDS-MLD unclassifiable. Myelodysplastic syndrome (MDS) with multilineage dysplasia (MDS-MLD), is an MDS characterized by one or more cytopenias and dysplastic changes in two or more of the myeloid lineages (i.e., erythroid, granulocytic, and megakaryocytic). The bone marrow, in particular, showed prominent dysplasia, including the presence of atypical megakaryocytes with small hypolobated morphology reminiscent of those typically seen in MDS with isolated 5q deletion. Cytogenetic analysis, including interphase and metaphase FISH, karyotype and SNP chromosomal microarray were performed, as well as DNA sequencing studies. Cytogenetic analysis showed a very complex karyotype featuring multiple 5q intrachromosomal rearrangements including a pericentric inversion with multiple interspersed deletions and monosomy 7. FISH studies showed a partial deletion of the PDGFRβ gene, and SNP chromosomal microarray and targeted panel-based sequencing identified biallelic loss of function of the TP53 gene. Based on the pathologic findings, the patient was treated for MDS but did not respond to either lenalidomide or azacitidine.</p><p><strong>Conclusion: </strong>The genetic changes described, in particular, the complex intrachromosomal rearrangements of chromosome 5, suggest the occurrence of a sudden catastrophic event that led to an aggressive course in the patient's disease. Conventional karyotyping, metaphase and interphase FISH, SNP chromosomal microarray and NGS helped to identify the complex genetic changes seen in this case. This highlights the importance of utilizing a multimodality approach to fully characterize complex chromosomal events that may significantly impact disease progression, treatment and survival.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"15 1","pages":"51"},"PeriodicalIF":1.3,"publicationDate":"2022-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10430525","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}