Molecular Cytogenetics最新文献

{"title":"Long-read sequencing unmasks a cryptic three-way translocation resulting in an ETV6::PDGFRB fusion.","authors":"Joseph Tripodi, Douglas Tremblay, Daiva Ahire, Vesna Najfeld","doi":"10.1186/s13039-025-00730-7","DOIUrl":"10.1186/s13039-025-00730-7","url":null,"abstract":"<p><strong>Background: </strong>Myeloid/Lymphoid Neoplasms (MLN) with eosinophilia and PDGFRB rearrangements are rare but distinct hematologic malignancies driven by the constitutive activation of the PDGFRB tyrosine kinase through gene fusions. These neoplasms are sensitive to tyrosine kinase inhibitors (TKIs) such as imatinib, which often leads to rapid and durable molecular remissions. However, diagnostic challenges frequently arise from cryptic rearrangements, necessitating comprehensive molecular approaches.</p><p><strong>Case presentation: </strong>A 37-year-old male patient initially presented with pancytopenia and a splenic infarct; subsequent bone marrow findings were suggestive of a myeloid/lymphoid neoplasm. Initial conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) identified a PDGFRB gene rearrangement but were unable to fully resolve the structural complexity of the underlying genomic alteration. Long-read sequencing helped resolve a complex three-way translocation involving chromosomes 5, 12, and 20, precisely defining the ETV6::PDGFRB fusion with base pair resolution, and identified the partner gene (KAT14) on chromosome 20p. Following the diagnosis, the patient was started on imatinib therapy and has since achieved clinical and hematological improvement.</p><p><strong>Conclusion: </strong>This case highlights the significant diagnostic utility of long-read sequencing in uncovering and characterizing cryptic and complex genomic rearrangements that are frequently missed by conventional methods. Accurate molecular characterization is critical for disease classification, guiding targeted therapeutic decisions, and ultimately improving patient outcomes in PDGFRB-rearranged neoplasms.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"28"},"PeriodicalIF":1.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346330","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":"Cytogenomics and optical genome mapping approaches characterize a derivative interstitial monosomy 18p due to a maternal complex intrachromosomal rearrangement.","authors":"Ludovico Graziani, Silvia Genovese, Maria Luce Genovesi, Cristiana Di Rosa, Rosalba Di Noi, Sara Loddo, Mario Bengala, Vito Luigi Colona, Antonio Novelli, Giuseppe Novelli, Viola Alesi, Anna Maria Nardone","doi":"10.1186/s13039-025-00732-5","DOIUrl":"10.1186/s13039-025-00732-5","url":null,"abstract":"<p><strong>Background: </strong>Monosomy 18p (MIM: 146390) is a well-known chromosomal disorder associated with intellectual disability, short stature, and non-specific craniofacial features resulting from partial or total deletion of the short arm of chromosome 18. The differential diagnosis is broad due to nonspecific and variable phenotypes. The majority of 18p monosomy cases result from de novo deletions, while the remainder are either caused by de novo translocation with loss of 18p, malsegregation of a parental translocation or inversion, or the presence of a ring chromosome or isochromosome 18q. Establishing the etiopathogenetic mechanism is essential to properly assess the risk of recurrence. Chromosomal Microarray Analysis (CMA) has enabled better genotype-phenotype correlations. Nonetheless, CMA is not appropriate for characterizing complex or balanced structural variants, which may underlie complex rearrangement, and the resolution of karyotype analysis is limited.</p><p><strong>Case presentation: </strong>Here, we report the first case of a derivative 18p interstitial monosomy caused by a maternal complex intrachromosomal rearrangement, fully characterized by Optical Genome Mapping (OGM).</p><p><strong>Conclusions: </strong>This rearrangement could not be fully characterized by either CMA or karyotype analyses, both of which yielded only partial and inconclusive results. The integration of OGM into routine diagnostics could enhance the understanding of complex chromosomal rearrangements, leading to improved prognostic and reproductive risk assessment.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"27"},"PeriodicalIF":1.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293114","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 1q21.1 microdeletions and microduplications: a retrospective case series.","authors":"Ziyang Liu, Song Yi, Manman Li, Nian Liu","doi":"10.1186/s13039-025-00731-6","DOIUrl":"10.1186/s13039-025-00731-6","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize the prenatal features, inheritance patterns, and outcomes of 1q21.1 copy number variations (CNVs) and refine prenatal counseling strategies.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 20 consecutive prenatal cases diagnosed with 1q21.1 CNVs between 2017 and 2024. Genetic testing included karyotyping, chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq). Phenotypic data, inheritance patterns, and pregnancy outcomes were evaluated.</p><p><strong>Results: </strong>The cohort comprised 12 microdeletions (60%) and 8 microduplications (40%). Ultrasound anomalies were detected in 66.7% (8/12) of microdeletion cases (e.g., fetal growth restriction, cardiac defects) and 37.5% (3/8) of microduplication cases (e.g., nasal bone hypoplasia). No specific prenatal ultrasound markers pathognomonic for 1q21.1 CNVs were identified. Termination of pregnancy (TOP) was elected in 50% (10/20) of cases, predominantly for de novo CNVs (80% of TOP decisions). Among live-born infants (n = 9), no overt abnormalities were detected during postnatal follow-up (3 months to 5 years).</p><p><strong>Conclusion: </strong>Prenatal 1q21.1 CNVs demonstrate incomplete penetrance and variable expressivity, without consistent association with specific prenatal ultrasound markers. The TOP rate for de novo CNVs reflects profound parental anxiety regarding neurodevelopmental outcomes. These findings underscore the critical need for comprehensive prenatal counseling that integrates genomic findings, phenotypic severity, and psychosocial support.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"23"},"PeriodicalIF":1.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200407","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":"Isodicentric Y chromosome with SRY duplication in a female with complete gonadal dysgenesis.","authors":"Arash Salmaninejad, Zahra Yaghoubi, Tahereh Haghzad, Maryam Latifi, Reza Bayat, Somaye Esnaashari, Setila Dalili","doi":"10.1186/s13039-025-00728-1","DOIUrl":"10.1186/s13039-025-00728-1","url":null,"abstract":"<p><strong>Background: </strong>Sexual differentiation and development rely upon many genetic and environmental factors and any disruption of these can lead to Differences/Disorders of Sex Development (DSDs). DSDs are a diverse group of heterogeneous rare diseases that can be categorized into three main groups. 46,XY, complete gonadal dysgenesis is a subgroup of 46,XY, DSD that appears as female phenotype and external genitalia characterized by primary amenorrhea at adolescent.</p><p><strong>Case presentation: </strong>Here, we present a 14-year-old female patient with structural rearrangements of the Y chromosome including SRY gene duplication. These chromosomes were characterized by karyotyping, Oligo-array comparative genomic hybridization (CGH), metaphase fluorescence in situ hybridization (FISH), and exome sequencing (ES). The mechanism(s) by which these rearrangements could have occurred is discussed.</p><p><strong>Conclusions: </strong>46,X, idic(Y)(p11.32→q11.22:: q11.22→p11.32)] in this proband led to a large copy-number change including 24.5 Mb gain on the Yp11.32q11.223 region and a 33 Mb loss on the Yq11.223q11.23 region.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"25"},"PeriodicalIF":1.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200425","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":"Rare single PML::RARA fusion transcript from insertion on derivative chromosome 17 in acute promyelocytic leukemia.","authors":"Ping Yang, Daniel Cassidy, Catalina Amador, Sangeetha Venugopal","doi":"10.1186/s13039-025-00727-2","DOIUrl":"10.1186/s13039-025-00727-2","url":null,"abstract":"<p><p>Over 90% of patients with acute promyelocytic leukemia (APL) harbor the typical translocation characterized by the dual fusion of PML::RARA and RARA::PML transcripts. Here, we report a case with a single fusion of PML::RARA formed on der(17), without the RARA::PML fusion, and the patient responded well to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) therapy. To our knowledge, this represents only the fourth reported case of this type. Our findings indicate that the PML::RARA fusion is the primary driver of APL leukemogenesis and the main therapeutic target for ATRA and ATO, suggesting that the RARA::PML transcript may not be essential for APL development.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"26"},"PeriodicalIF":1.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200439","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":"Genetic analysis of an asymptomatic female with a large Xp deletion revealed insights into the X chromosome inactivation pattern: a case report.","authors":"Li-Jun Zhang, Wen-Lan Liu, Shu-Yi Shao, Yong Xu, Lu Zhou","doi":"10.1186/s13039-025-00729-0","DOIUrl":"10.1186/s13039-025-00729-0","url":null,"abstract":"<p><strong>Background: </strong>X-linked disorders caused by skewed X chromosome inactivation (XCI) result in phenotypic heterogeneity, which is rarely reported. XCI testing is not widely used in clinical cases, making risk assessment for carriers of X-linked unbalanced structural abnormalities challenging.</p><p><strong>Case presentation: </strong>We present genetic data from an asymptomatic female with a de novo 6.31 Mb deletion on Xp11.23-p11.22, identified through CMA-array analysis. The deletion includes 101 OMIM genes, 11 haplo-insufficient (HI) genes, and 4 escape genes. An androgen receptor (AR) methylation assay showed a 100% skewed XCI pattern silencing the abnormal X-chromosome. RNA-seq analysis revealed up-regulation of escape genes within the deletion at the transcriptional level. The absence of a severe clinical phenotype, aside from infertility, in this female was most likely attributed to the extremely skewed XCI and the compensatory up-regulation of XCI escape genes.</p><p><strong>Conclusions: </strong>Our data indicate that XCI can modify the phenotype in female carriers of heterozygous X-linked deletion and provide valuable information about the analysis of XCI pattern in risk assessment of this kind cases, especially precious fetuses.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"24"},"PeriodicalIF":1.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200430","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":"Maternal uniparental disomy of chromosome 15 with concurrent paternal non-chromosome 15 marker chromosome: a rare presentation of prader-willi syndrome.","authors":"Yang Nannan, Yang Yang, Wang Yan, Wang Hao","doi":"10.1186/s13039-025-00726-3","DOIUrl":"10.1186/s13039-025-00726-3","url":null,"abstract":"<p><strong>Background: </strong>Prader-Willi Syndrome (PWS) is a complicated genetic disorder demonstrating a variety of clinical phenotypes. Using molecular cytogenetics approaches to detect the deletions of the paternal 15q11-q13 region and maternal uniparental disomy of chromosome 15 plays an important role in the prenatal diagnosis of PWS.</p><p><strong>Case presentation: </strong>A pregnant woman with advanced maternal age underwent amniocentesis. The amniotic fluid was subjected to karyotyping and chromosomal microarray analysis. A marker without autosomal material and loss of heterozygosity (LOH) of 15q14-q23 were found in the fetus. The LOH was consistent with maternal uniparental isodisomy (UPD) and the marker was inherited from the father. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) found increased methylation in the fetal 15q11.2-q13 region and fluorescence in situ hybridization confirmed the marker was not originated from chromosome 15.</p><p><strong>Conclusion: </strong>We presented a rare PWS case showing maternal UPD of chromosome 15 with concurrent paternal marker chromosome in the prenatal setting.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"22"},"PeriodicalIF":1.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962384","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":"Potential role of SLC6A3 in neurodevelopmental impairments associated with corpus callosum abnormalities: insights from CNV analysis and clinical phenotyping.","authors":"Shan-Yu Liu, Wei Huang, Hui-Lin Ou, Li Wang, Dan-Dan Wang, Wei-He Tan, Qin She","doi":"10.1186/s13039-025-00725-4","DOIUrl":"10.1186/s13039-025-00725-4","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the role of pathogenic copy number variations (CNVs) in neurodevelopmental impairments among children with corpus callosum abnormalities (CCAs). We focused primarily on SLC6A3 associated mechanisms and aimed to delineate genotype-phenotype correlations in our cases.</p><p><strong>Methods: </strong>From January 2021 to July 2023, 13 children with MRI-confirmed CCAs underwent chromosomal microarray analysis (CMA) for CNV detection. We performed bioinformatic analyses (Gene Ontology, STRING network) to identify neurodevelopmental genes within pathogenic CNVs, and clinical follow up assessed neurobehavioral outcomes.</p><p><strong>Results: </strong>We identified pathogenic CNVs in 3/13 cases (23.08%). Specifically, Case 8 harbored a 43.05-Mb duplication (5p15.33p12) encompassing SLC6A3, a dopamine transporter gene linked to synaptic signaling. Interaction network analysis suggested that SLC6A3 was the most interconnected gene, providing evidence of its role in CCAs. Clinically, 84.6% of cases (11/13) exhibited psychomotor delay, while 15.4% of cases (2/13) developed seizure. Notably, we observed hearing impairment and psychomotor developmental delay in Case 8 with a SLC6A3 duplication, further suggesting dopaminergic dysregulation in callosal connectivity.</p><p><strong>Conclusion: </strong>Our study suggests that SLC6A3 may represent a potential contributor to neurodevelopmental impairments in CCAs. Further, CMA-based CNV screening is critical for early intervention in high-risk children. These findings bridge genetic etiology with clinical phenotypes and offer insights into future targeted therapeutic strategies.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"18 1","pages":"21"},"PeriodicalIF":1.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962330","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":"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":"","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}