Molecular Cytogenetics最新文献

{"title":"Two cases of placental trisomy 21 mosaicism causing false-negative NIPT results.","authors":"Qinfei Zhao,&nbsp;Jing Chen,&nbsp;Ling Ren,&nbsp;Huijuan Zhang,&nbsp;Dedong Liu,&nbsp;Xuxiang Xi,&nbsp;Xiangsheng Wu,&nbsp;Chunyun Fang,&nbsp;Ping Ye,&nbsp;Shaoying Zeng,&nbsp;Tianyu Zhong","doi":"10.1186/s13039-023-00643-3","DOIUrl":"https://doi.org/10.1186/s13039-023-00643-3","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive prenatal testing (NIPT) using cell-free DNA has been widely used for prenatal screening to detect the common fetal aneuploidies (such as trisomy 21, 18, and 13). NIPT has been shown to be highly sensitive and specific in previous studies, but false positives (FPs) and false negatives (FNs) occur. Although the prevalence of FN NIPT results for Down syndrome is rare, the impact on families and society is significant.</p><p><strong>Case presentation: </strong>This article described two cases of foetuses that tested \"negative\" for trisomy 21 by NIPT technology using the semiconductor sequencing platform. However, the fetal karyotypes of amniotic fluid were 46,XY, + 21 der(21;21)(q10;q10) and 47,XY, + 21 karyotypes, respectively. Placental biopsies confirmed that, in the first case, the chromosome 21 placenta chimerism ratio ranged from 13 to 88% with the 46,XX, + 21,der(21;21)(q10;q10)[86]/46,XX[14] karyotype of placental chorionic cells (middle of fetal-side placental tissue). However, in the second case, of all the placental biopsies, percentage of total chimerism was less than 30%; and placental biopsies taken at the middle of maternal side and middle of fetal side, also had variable trisomy 2 mosaicism levels of 10% and 8%, respectively. Ultimately, the pregnancies were interrupted at 30 gestational age (GA) and 27GA, respectively.</p><p><strong>Conclusions: </strong>In this study, we present two cases of FN NIPT results that might have been caused by biological mechanisms, as opposed to poor quality, technical errors, or negligence. Clinical geneticists and their patients must understand that NIPT is a screening procedure.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"16"},"PeriodicalIF":1.3,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814539","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":"17q25.3 copy number changes: association with neurodevelopmental disorders and cardiac malformation.","authors":"Nikhil Shri Sahajpal,&nbsp;David H F Jeffrey,&nbsp;Barbara R DuPont,&nbsp;Benjamin Hilton","doi":"10.1186/s13039-023-00644-2","DOIUrl":"https://doi.org/10.1186/s13039-023-00644-2","url":null,"abstract":"<p><p>Copy number variants (CNVs) have been identified as common genomic variants that play a significant role in inter-individual variability. Conversely, rare recurrent CNVs have been found to be causal for many disorders with well-established genotype-phenotype relationships. However, the phenotypic implications of rare non-recurrent CNVs remain poorly understood. Herein, we re-investigated 18,542 cases reported from chromosomal microarray at Greenwood Genetic Center from 2010 to 2022 and identified 15 cases with CNVs involving the 17q25.3 region. We report the detailed clinical features of these subjects, and compare with the cases reported in the literature to determine genotype-phenotype correlations for a subset of genes in this region. The CNVs in the 17q25.3 region were found to be rare events, with a prevalence of 0.08% (15/18542) observed in our cohort. The CNVs were dispersed across the entire 17q25.3 region with variable breakpoints and no smallest region of overlap. The subjects presented with a wide range of clinical features, with neurodevelopmental disorders (autism spectrum disorder, intellectual disability, developmental delay) being the most common features (80%), then expressive language disorder (33%), and finally cardiovascular malformations (26%). The association of CNVs involving the critical gene-rich region of 17q25.3 with neurodevelopmental disorders and cardiac malformation, implicates several genes as plausible drivers for these events.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"15"},"PeriodicalIF":1.3,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9813627","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":"Genome-wide detection of CNV regions between Anqing six-end-white and Duroc pigs.","authors":"Rong Qian,&nbsp;Fei Xie,&nbsp;Wei Zhang,&nbsp;JuanJuan Kong,&nbsp;Xueli Zhou,&nbsp;Chonglong Wang,&nbsp;Xiaojin Li","doi":"10.1186/s13039-023-00646-0","DOIUrl":"https://doi.org/10.1186/s13039-023-00646-0","url":null,"abstract":"<p><strong>Background: </strong>Anqing six-end-white pig is a native breed in Anhui Province. The pigs have the disadvantages of a slow growth rate, low proportion of lean meat, and thick back fat, but feature the advantages of strong stress resistance and excellent meat quality. Duroc pig is an introduced pig breed with a fast growth rate and high proportion of lean meat. With the latter breed featuring superior growth characteristics but inferior meat quality traits, the underlying molecular mechanism that causes these phenotypic differences between Chinese and foreign pigs is still unclear.</p><p><strong>Results: </strong>In this study, copy number variation (CNV) detection was performed using the re-sequencing data of Anqing Six-end-white pigs and Duroc pigs, A total of 65,701 CNVs were obtained. After merging the CNVs with overlapping genomic positions, 881 CNV regions (CNVRs) were obtained. Based on the obtained CNVR information combined with their positions on the 18 chromosomes, a whole-genome map of the pig CNVs was drawn. GO analysis of the genes in the CNVRs showed that they were primarily involved in the cellular processes of proliferation, differentiation, and adhesion, and primarily involved in the biological processes of fat metabolism, reproductive traits, and immune processes.</p><p><strong>Conclusion: </strong>The difference analysis of the CNVs between the Chinese and foreign pig breeds showed that the CNV of the Anqing six-end-white pig genome was higher than that of the introduced pig breed Duroc. Six genes related to fat metabolism, reproductive performance, and stress resistance were found in genome-wide CNVRs (DPF3, LEPR, MAP2K6, PPARA, TRAF6, NLRP4).</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"12"},"PeriodicalIF":1.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301708","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":"Characteristics and mechanisms of mosaicism in prenatal diagnosis cases by application of SNP array.","authors":"Lili Zhou,&nbsp;Huanzheng Li,&nbsp;Chenyang Xu,&nbsp;Xueqin Xu,&nbsp;Zhaoke Zheng,&nbsp;Shaohua Tang","doi":"10.1186/s13039-023-00648-y","DOIUrl":"https://doi.org/10.1186/s13039-023-00648-y","url":null,"abstract":"<p><strong>Background: </strong>With the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof.</p><p><strong>Results: </strong>Using SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1.0%. The prevalence of mosaicism was 4.1% for chorionic villus sample, 0.4% for amniotic fluid, and 1.3% for umbilical cord blood. Of these cases, 29 were mosaic aneuploidy and 15 were mosaic segmental duplication/deletion. Three cases of mosaic trisomy 16 and three cases of mosaic trisomy 22 were diagnosed in the CVS samples, while four cases of mosaic trisomy 21 were detected in amniotic fluid and umbilical cord blood samples. The distribution pattern of mosaicism suggested trisomy rescue as the underlying mechanism. Structurally rearranged chromosomes were observed, including three cases with supernumerary marker chromosomes, three cases with dicentric chromosomes, and one case with a ring chromosome. All mosaic segmental duplication/deletion cases were the result of mitotic non-disjunction, with the exception of one case involving mosaic11q segmental duplication.</p><p><strong>Conclusion: </strong>Improved utilization of SNP arrays enables the characterization of mosaicism and facilitates the estimation of disease mechanisms and recurrence.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"13"},"PeriodicalIF":1.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9742295","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":"BCR::ABL1-like acute lymphoblastic leukaemia: a single institution experience on identification of potentially therapeutic targetable cases.","authors":"Anna Płotka,&nbsp;Anna Przybyłowicz-Chalecka,&nbsp;Maria Korolczuk,&nbsp;Zuzanna Kanduła,&nbsp;Błażej Ratajczak,&nbsp;Jolanta Kiernicka-Parulska,&nbsp;Anna Mierzwa,&nbsp;Katarzyna Godziewska,&nbsp;Małgorzata Jarmuż-Szymczak,&nbsp;Lidia Gil,&nbsp;Krzysztof Lewandowski","doi":"10.1186/s13039-023-00645-1","DOIUrl":"https://doi.org/10.1186/s13039-023-00645-1","url":null,"abstract":"<p><strong>Background: </strong>BCR::ABL1-like acute lymphoblastic leukaemia (BCR::ABL1-like ALL) is characterized by inferior outcomes. Current efforts concentrate on the identification of molecular targets to improve the therapy results. The accessibility to next generation sequencing, a recommended diagnostic method, is limited. We present our experience in the BCR::ABL1-like ALL diagnostics, using a simplified algorithm.</p><p><strong>Results: </strong>Out of 102 B-ALL adult patients admitted to our Department in the years 2008-2022, 71 patients with available genetic material were included. The diagnostic algorithm comprised flow cytometry, fluorescent in-situ hybridization, karyotype analysis and molecular testing with high resolution melt analysis and Sanger Sequencing. We recognized recurring cytogenetic abnormalities in 32 patients. The remaining 39 patients were screened for BCR::ABL1-like features. Among them, we identified 6 patients with BCR::ABL1-like features (15.4%). Notably, we documented CRLF2-rearranged (CRLF2-r) BCR::ABL1-like ALL occurrence in a patient with long-term remission of previously CRLF2-r negative ALL.</p><p><strong>Conclusions: </strong>An algorithm implementing widely available techniques enables the identification of BCR::ABL1-like ALL cases in settings with limited resources.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"14"},"PeriodicalIF":1.3,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132309","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":"Novel maternal duplication of 6p22.3-p25.3 with subtelomeric 6p25.3 deletion: new clinical findings and genotype-phenotype correlations.","authors":"Liyu Zhang,&nbsp;Xiaoling Tie,&nbsp;Fengyu Che,&nbsp;Guoxia Wang,&nbsp;Ying Ge,&nbsp;Benchang Li,&nbsp;Ying Yang","doi":"10.1186/s13039-023-00640-6","DOIUrl":"https://doi.org/10.1186/s13039-023-00640-6","url":null,"abstract":"<p><strong>Background: </strong>Copy-number variants (CNVs) drive many neurodevelopmental-related disorders. Although many neurodevelopmental-related CNVs can give rise to widespread phenotypes, it is necessary to identify the major genes contributing to phenotypic presentation. Copy-number variations in chromosome 6, such as independent 6p deletion and 6p duplication, have been reported in several live-born infants and present widespread abnormalities such as intellectual disability, growth deficiency, developmental delay, and multiple dysmorphic facial features. However, a contiguous deletion and duplication in chromosome 6p regions have been reported in only a few cases.</p><p><strong>Case presentation: </strong>In this study, we reported the first duplication of chromosome band 6p25.3-p22.3 with deletion of 6p25.3 in a pedigree. This is the first case reported involving CNVs in these chromosomal regions. In this pedigree, we reported a 1-year-old boy with maternal 6p25-pter duplication characterized by chromosome karyotype. Further analysis using CNV-seq revealed a 20.88-Mb duplication at 6p25.3-p22.3 associated with a contiguous 0.66-Mb 6p25.3 deletion. Whole exome sequencing confirmed the deletion/duplication and identified no pathogenic or likely pathogenic variants related with the patient´s phenotype. The proband presented abnormal growth, developmental delay, skeletal dysplasia, hearing loss, and dysmorphic facial features. Additionally, he presented recurrent infection after birth. CNV-seq using the proband´s parental samples showed that the deletion/duplication was inherited from the proband´s mother, who exhibited a similar phenotype to the proband. When compared with other cases, this proband and his mother presented a new clinical finding: forearm bone dysplasia. The major candidate genes contributing to recurrent infection, eye development, hearing loss features, neurodevelopmental development, and congenital bone dysplasia were further discussed.</p><p><strong>Conclusions: </strong>Our results showed a new clinical finding of a contiguous deletion and duplication in chromosome 6p regions and suggested candidate genes associated with phenotypic features, such as FOXC1, SERPINB6, NRN1, TUBB2A, IRF4, and RIPK1.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"11"},"PeriodicalIF":1.3,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9618022","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":"Laboratory performance of genome-wide cfDNA for copy number variants as compared to prenatal microarray.","authors":"Erica Soster,&nbsp;John Tynan,&nbsp;Clare Gibbons,&nbsp;Wendy Meschino,&nbsp;Jenna Wardrop,&nbsp;Eyad Almasri,&nbsp;Stuart Schwartz,&nbsp;Graham McLennan","doi":"10.1186/s13039-023-00642-4","DOIUrl":"https://doi.org/10.1186/s13039-023-00642-4","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive prenatal testing (NIPT) allows for screening of fetal aneuploidy and copy number variants (CNVs) from cell-free DNA (cfDNA) in maternal plasma. Professional societies have not yet embraced NIPT for fetal CNVs, citing a need for additional performance data. A clinically available genome-wide cfDNA test screens for fetal aneuploidy and CNVs larger than 7 megabases (Mb).</p><p><strong>Results: </strong>This study reviews 701 pregnancies with \"high risk\" indications for fetal aneuploidy which underwent both genome-wide cfDNA and prenatal microarray. For aneuploidies and CNVs considered 'in-scope' for the cfDNA test (CNVs ≥ 7 Mb and select microdeletions), sensitivity and specificity was 93.8% and 97.3% respectively, with positive and negative predictive values of 63.8% and 99.7% as compared to microarray. When including 'out-of-scope' CNVs on array as false negatives, the sensitivity of cfDNA falls to 48.3%. If only pathogenic out-of-scope CNVs are treated as false negatives, the sensitivity is 63.8%. Of the out-of-scope CNVs identified by array smaller than 7 Mb, 50% were classified as variants of uncertain significance (VUS), with an overall VUS rate in the study of 2.29%.</p><p><strong>Conclusions: </strong>While microarray provides the most robust assessment of fetal CNVs, this study suggests that genome-wide cfDNA can reliably screen for large CNVs in a high-risk cohort. Informed consent and adequate pretest counseling are essential to ensuring patients understand the benefits and limitations of all prenatal testing and screening options.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"10"},"PeriodicalIF":1.3,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991887","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":"Preimplantation genetic testing for Aicardi-Goutières syndrome induced by novel compound heterozygous mutations of TREX1: an unaffected live birth.","authors":"Huiling Xu,&nbsp;Jiajie Pu,&nbsp;Suiling Lin,&nbsp;Rui Hu,&nbsp;Jilong Yao,&nbsp;Xuemei Li","doi":"10.1186/s13039-023-00641-5","DOIUrl":"https://doi.org/10.1186/s13039-023-00641-5","url":null,"abstract":"<p><strong>Background: </strong>Aicardi-Goutières syndrome (AGS) is a rare, autosomal recessive, hereditary neurodegenerative disorder. It is characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Preimplantation genetic testing (PGT) is a procedure that could be used to choose unaffected embryos for transfer after analysis of biopsied cells, which prevents at-risk couples from facing the risk of pregnancy termination.</p><p><strong>Methods: </strong>Trio-based whole exome sequencing, karyotyping and chromosomal microarray analysis were used to determine the pathogenic mutations for the family. To block the inheritance of the disease, multiple annealing and looping-based amplification cycles was used for whole genome amplification of the biopsied trophectoderm cells. Sanger sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used to detect the state of the gene mutations. Copy number variation (CNV) analysis was also carried out to prevent embryonic chromosomal abnormalities. Prenatal diagnosis was preformed to verify the PGT outcomes.</p><p><strong>Results: </strong>A novel compound heterozygous mutation in TREX1 gene was found in the proband causing AGS. A total of 3 blastocysts formed after intracytoplasmic sperm injection were biopsied. After genetic analyses, an embryo harbored a heterozygous mutation in TREX1 and without CNV was transferred. A healthy baby was born at 38th weeks and prenatal diagnosis results confirmed the accuracy of PGT.</p><p><strong>Conclusions: </strong>In this study, we identified two novel pathogenic mutations in TREX1, which has not been previously reported. Our study extends the mutation spectrum of TREX1 gene and contributes to the molecular diagnosis as well as genetic counseling for AGS. Our results demonstrated that combining NGS-based SNP haplotyping for PGT-M with invasive prenatal diagnosis is an effective approach to block the transmission of AGS and could be applied to prevent other monogenic diseases.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"9"},"PeriodicalIF":1.3,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9946658","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":"Hereditary multiple exostoses caused by a chromosomal inversion removing part of EXT1 gene.","authors":"Angelos Alexandrou,&nbsp;Nicole Salameh,&nbsp;Ioannis Papaevripidou,&nbsp;Nayia Nicolaou,&nbsp;Panayiotis Myrianthopoulos,&nbsp;Andria Ketoni,&nbsp;Ludmila Kousoulidou,&nbsp;Anna-Maria Anastasiou,&nbsp;Paola Evangelidou,&nbsp;George A Tanteles,&nbsp;Carolina Sismani","doi":"10.1186/s13039-023-00638-0","DOIUrl":"https://doi.org/10.1186/s13039-023-00638-0","url":null,"abstract":"<p><strong>Background: </strong>Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder characterized by the development of multiple, circumscript and usually symmetric bony protuberances called osteochondromas. Most HME are caused by EXT1 and EXT2 loss of function mutations. Most pathogenic mutations are nonsense followed by missense mutations and deletions.</p><p><strong>Case presentation: </strong>Here we report on a patient with a rare and complex genotype resulting in a typical HME phenotype. Initial point mutation screening in EXT1 and EXT2 genes by Sanger sequencing did not reveal any pathogenic variants. The patient along with the healthy parents was subsequently referred for karyotype and array-Comparative Genomic Hybridization (CGH) analyses. Chromosomal analysis revealed two independent de novo apparently balanced rearrangements: a balanced translocation between the long arms of chromosomes 2 and 3 at breakpoints 2q22 and 3q13.2 and a pericentric inversion with breakpoints at 8p23.1q24.1. Both breakpoints were confirmed by Fluorescence In Situ Hybridization (FISH). Subsequently, array-CGH revealed a novel heterozygous deletion within the EXT1 gene at one of the inversion breakpoints, rendering the inversion unbalanced. The mode of inheritance, as well as the size of the deletion were further investigated by Quantitative Real-time PCR (qPCR), defining the deletion as de novo and of 3.1 kb in size, removing exon 10 of EXT1. The inversion in combination with the 8p23.1 deletion most likely abolishes the transcription of EXT1 downstream of exon 10 hence resulting in a truncated protein.</p><p><strong>Conclusions: </strong>The identification of a rare and novel genetic cause of HME, highlights the importance of additional comprehensive investigation of patients with typical clinical manifestations, even when EXT1 and EXT2 mutation analysis is negative.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"16 1","pages":"8"},"PeriodicalIF":1.3,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9520974","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":"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}