Molecular Cytogenetics最新文献

{"title":"Molecular combing and its application in clinical settings.","authors":"Yiping Wang,&nbsp;Kishore Ramesh Kumar,&nbsp;Thomas Liehr","doi":"10.1186/s13039-022-00628-8","DOIUrl":"https://doi.org/10.1186/s13039-022-00628-8","url":null,"abstract":"<p><p>Molecular combing technology (MCT) is an effective means for stretching DNA molecules and making them thus accessible for in situ studies. MCT uses the force exerted in the process of liquid flow via surface tension to stretch DNA molecules and spread them on solid surfaces, i.e. glass cover slips. Many DNA molecules can be stretched at the same time in parallel and neatly arranged side-by-side, making the approach convenient for statistical analysis. Accordingly, DNA replication and transcription can be studied at the single molecule level. In this paper, the principle, experimental methods, important applications, advantages and shortcuts of MCT in medical field are presented and discussed.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"50"},"PeriodicalIF":1.3,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40689233","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 genetic counseling of an inherited Xq24q25 deletion associated with normal phenotype.","authors":"Yaqing Zhou, Mingxi Zhang, Yanmin Zhu, Qi Zhao","doi":"10.1186/s13039-022-00626-w","DOIUrl":"10.1186/s13039-022-00626-w","url":null,"abstract":"<p><strong>Background: </strong>Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. CNVs identified in prenatal cases need careful considerations and correct interpretation if those are harmless or harmful variants from the norm.</p><p><strong>Case presentation: </strong>A 28-year-old, gravida 1, para 0, woman underwent amniocentesis at 17 weeks of gestation because the noninvasive prenatal testing (NIPT) results revealed a 9.8 Mb deletion from Xq24 to Xq25. GTG-banding karyotype analysis was performed on cultured amniocytes. Chromosomal microarray analysis (CMA) on uncultured amniocytes was performed.</p><p><strong>Results: </strong>Chromosomal GTG-banding of the cultured amniocytes revealed a karyotype of 46,XX. CMA detected a 9.5-Mb chromosomal deletion in the region of Xq24q25 (arr[GRCh37] Xq24q25(118,975,436_128,444,692) × 1).</p><p><strong>Conclusion: </strong>The present report highlights that an integration of prenatal ultrasound, NIPT, karyotype analysis, CMA and genetic counseling is helpful for the prenatal diagnosis of chromosomal deletions/duplications.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"49"},"PeriodicalIF":1.3,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40679345","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":"Haploinsufficiencies of FOXF1, FOXC2 and FOXL1 genes originated from deleted 16q24.1q24.2 fragment related with alveolar capillary dysplasia with misalignment of pulmonary veins and lymphedema-distichiasis syndrome: relationship to phenotype.","authors":"Xuezhen Wang,&nbsp;Lili Guo,&nbsp;Bei Zhang,&nbsp;Jiebin Wu,&nbsp;Yu Sun,&nbsp;Huimin Tao,&nbsp;Jing Sha,&nbsp;Jingfang Zhai,&nbsp;Min Liu","doi":"10.1186/s13039-022-00627-9","DOIUrl":"https://doi.org/10.1186/s13039-022-00627-9","url":null,"abstract":"<p><strong>Objective: </strong>We describe a fetus with a 2.12-Mb terminal deleted fragment in 16q associated with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) and lymphedema-distichiasis syndrome (LDS) and intend to provide a comprehensive prenatal management strategy for the fetuses with ACDMPV and LDS through reviewing other similar published studies.</p><p><strong>Methods: </strong>The fetus presented a series of diverse structural malformations including congenital cardiovascular, genitourinary and gastro-intestinal anomalies in ultrasound at 23 + 5 weeks of gestation (GA). Amniocentesis was conducted for karyotype analysis and copy number variation sequencing (CNV-seq) after informed consent.</p><p><strong>Results: </strong>The fetal karyotype was 46,XX, however the result of CNV-seq showed an approximately 2.12-Mb deletion in 16q24.1q24.2 (85220000-87340000) × 1 indicating pathogenicity.</p><p><strong>Conclusion: </strong>Genomic testing should be recommend as a first line diagnostic tool for suspected ACDMPV and/or LDS or other genetic syndromes for the fetuses with structural abnormalities in clinical practice.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"48"},"PeriodicalIF":1.3,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446163","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":"Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort.","authors":"Anna Lengyel,&nbsp;Éva Pinti,&nbsp;Henriett Pikó,&nbsp;Árvai Kristóf,&nbsp;Tünde Abonyi,&nbsp;Zaránd Némethi,&nbsp;György Fekete,&nbsp;Irén Haltrich","doi":"10.1186/s13039-022-00623-z","DOIUrl":"https://doi.org/10.1186/s13039-022-00623-z","url":null,"abstract":"<p><strong>Background: </strong>Neurodevelopmental disorders are genetically heterogeneous pediatric conditions. The first tier diagnostic method for uncovering copy number variations (CNVs), one of the most common genetic etiologies in affected individuals, is chromosomal microarray (CMA). However, this methodology is not yet a routine molecular cytogenetic test in many parts of the world, including Hungary. Here we report clinical and genetic data of the first, relatively large Hungarian cohort of patients whose genetic testing included CMA.</p><p><strong>Methods: </strong>Clinical data were retrospectively collected for 78 children who were analyzed using various CMA platforms. Phenotypes of patients with disease-causing variants were compared to patients with negative results using the chi squared/Fisher exact tests.</p><p><strong>Results: </strong>A total of 30 pathogenic CNVs were identified in 29 patients (37.2%). Postnatal growth delay (p = 0.05564), pectus excavatum (p = 0.07484), brain imaging abnormalities (p = 0.07848), global developmental delay (p = 0.08070) and macrocephaly (p = 0.08919) were more likely to be associated with disease-causing CNVs.</p><p><strong>Conclusion: </strong>Our results allow phenotypic expansion of 14q11.2 microdeletions encompassing SUPT16H and CHD8 genes. Variants of unknown significance (n = 24) were found in 17 patients. We provide detailed phenotypic and genetic data of these individuals to facilitate future classification efforts, and spotlight two patients with potentially pathogenic alterations. Our results contribute to unraveling the diagnostic value of rare CNVs.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"47"},"PeriodicalIF":1.3,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40441162","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":"Chromosomal instability (CIN) in HAP1 cell lines revealed by multiplex fluorescence in situ hybridisation (M-FISH)","authors":"R. Banerjee, C. Sotero-Caio, B. Fu, Fengtang Yang","doi":"10.1186/s13039-022-00625-x","DOIUrl":"https://doi.org/10.1186/s13039-022-00625-x","url":null,"abstract":"","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45958915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic mosaicism in the diseased brain.","authors":"Ivan Y Iourov,&nbsp;Svetlana G Vorsanova,&nbsp;Oxana S Kurinnaia,&nbsp;Sergei I Kutsev,&nbsp;Yuri B Yurov","doi":"10.1186/s13039-022-00624-y","DOIUrl":"https://doi.org/10.1186/s13039-022-00624-y","url":null,"abstract":"<p><p>It is hard to believe that all the cells of a human brain share identical genomes. Indeed, single cell genetic studies have demonstrated intercellular genomic variability in the normal and diseased brain. Moreover, there is a growing amount of evidence on the contribution of somatic mosaicism (the presence of genetically different cell populations in the same individual/tissue) to the etiology of brain diseases. However, brain-specific genomic variations are generally overlooked during the research of genetic defects associated with a brain disease. Accordingly, a review of brain-specific somatic mosaicism in disease context seems to be required. Here, we overview gene mutations, copy number variations and chromosome abnormalities (aneuploidy, deletions, duplications and supernumerary rearranged chromosomes) detected in the neural/neuronal cells of the diseased brain. Additionally, chromosome instability in non-cancerous brain diseases is addressed. Finally, theoretical analysis of possible mechanisms for neurodevelopmental and neurodegenerative disorders indicates that a genetic background for formation of somatic (chromosomal) mosaicism in the brain is likely to exist. In total, somatic mosaicism affecting the central nervous system seems to be a mechanism of brain diseases.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"45"},"PeriodicalIF":1.3,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40562380","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":"Observations on chromosome-specific sequencing for the construction of cross-species chromosome homology maps and its resolution of human:alpaca homology.","authors":"Malcolm A Ferguson-Smith,&nbsp;Jorge C Pereira,&nbsp;Ana Borges,&nbsp;Fumio Kasai","doi":"10.1186/s13039-022-00622-0","DOIUrl":"https://doi.org/10.1186/s13039-022-00622-0","url":null,"abstract":"<p><strong>Background: </strong>The history of comparative chromosome mapping is briefly reviewed, with discussion about the problem that occurs in chromosome painting when size heteromorphisms between homologues cause contamination in chromosomes sorted by flow cytometry that are used in the preparation of chromosome-specific DNA probes.</p><p><strong>Main body: </strong>As an example, we show in the alpaca (Vicagna pacos) that sequencing of contaminated chromosome sorts can reveal chromosome homologies from alignment with human and mouse genome reference sequences. The procedure identifies syntenic blocks of DNA separated in the human karyotype that are associated in the closely related alpaca and dromedary (Camelus dromedarius) karyotypes. This example provides proof of principal for the validity of the method for comparative chromosome mapping.</p><p><strong>Conclusion: </strong>It is suggested that the approach presented here may have application in the construction of comparative chromosome maps between distantly related taxa, such as monotremes and mammals.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"44"},"PeriodicalIF":1.3,"publicationDate":"2022-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512841","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 profile of adult acute myeloid leukemia in Egypt: a single-center experience.","authors":"Mohamed G Elnaggar,&nbsp;Eman Mosad,&nbsp;Ahmed Makboul,&nbsp;Engy Adel Shafik","doi":"10.1186/s13039-022-00621-1","DOIUrl":"https://doi.org/10.1186/s13039-022-00621-1","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a diverse disease characterized by the expansion of blasts of myeloid lineage. Cytogenetic testing is the cornerstone for risk stratification of AML patients. Geographical and environmental factors may play a very important role in the development of leukemia and several differences in genetic profile may be seen among different ethnicities. In our study, we evaluated cytogenetic findings of adult AML patients in South Egypt.</p><p><strong>Methods: </strong>Cytogenetic testing (karyotyping and M-FISH) was performed for 120 adult patients with AML. Twenty metaphases were analyzed for each patient.</p><p><strong>Results: </strong>In our study, the median age of AML patients was 36.5 years, with an age range between 18 and 86 years. 56.7% of patients had normal karyotypes and 43.3% of patients had clonal cytogenetic abnormalities. t (15;17) was the most detected structural abnormality, and + 8 was the most detected numerical abnormality. Regarding cytogenetic risk stratification, 65% of patients were in the intermediate-risk category.</p><p><strong>Conclusion: </strong>The cytogenetic profile of AML patients in our locality showed some differences and some similarities with cytogenetic profiles in different Arab, Asian and Western countries. Further studies are needed using advanced techniques such as next-generation sequencing and optical genome mapping to elucidate more ethnic and geographic genetic heterogeneity among different countries.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"43"},"PeriodicalIF":1.3,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33486971","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":"Clinical and molecular characterization of 1q43q44 deletion and corpus callosum malformations: 2 new cases and literature review.","authors":"Bochra Khadija,&nbsp;Khouloud Rjiba,&nbsp;Sarra Dimassi,&nbsp;Wafa Dahleb,&nbsp;Molka Kammoun,&nbsp;Hanen Hannechi,&nbsp;Najoua Miladi,&nbsp;Neziha Gouider-Khouja,&nbsp;Ali Saad,&nbsp;Soumaya Mougou-Zerelli","doi":"10.1186/s13039-022-00620-2","DOIUrl":"https://doi.org/10.1186/s13039-022-00620-2","url":null,"abstract":"<p><strong>Background: </strong>Corpus callosum malformations (CCM) represent one of the most common congenital cerebral malformations with a prevalence of around one for 4000 births. There have been at least 230 reports in the literature concerning 1q43q44 deletions of varying sizes discovered using chromosomal microarrays. This disorder is distinguished by global developmental delay, seizures, hypotonia, corpus callosum defects, and significant craniofacial dysmorphism. In this study, we present a molecular cytogenetic analysis of 2 Tunisian patients with corpus callosum malformations. Patient 1 was a boy of 3 years old who presented psychomotor retardation, microcephaly, behavioral problems, interventricular septal defect, moderate pulmonary stenosis, hypospadias, and total CCA associated with delayed encephalic myelination. Patient 2 was a boy of 9 months. He presented a facial dysmorphia, a psychomotor retardation, an axial hypotonia, a quadri pyramidal syndrome, a micropenis, and HCC associated with decreased volume of the periventricular white matter. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used.</p><p><strong>Results: </strong>Array CGH analysis reveals that patient 1 had the greater deletion size (11,7 Mb) at 1q43. The same region harbors a 2,7 Mb deletion in patient 2. Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. In both patients, the commonly deleted region includes six genes: PLD5, AKT3, ZNF238, HNRNPU, SDCCAG8 and CEP170. Based on the role of the ZNF238 gene in neuronal proliferation, migration, and cortex development, we hypothesized that the common deletion of ZNF238 in both patients seems to be the most responsible for corpus callosum malformations. Its absence may directly cause CCM. In addition, due to their high expression in the brain, PLD5 and FMN2 could modulate in the CCM phenotype.</p><p><strong>Conclusion: </strong>Our findings support and improve the complex genotype-phenotype correlations previously reported in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of several genes related to this pathology.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"42"},"PeriodicalIF":1.3,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9528098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33501215","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 a familial complex chromosomal rearrangement by optical genome mapping.","authors":"Yang Yang,&nbsp;Wang Hao","doi":"10.1186/s13039-022-00619-9","DOIUrl":"https://doi.org/10.1186/s13039-022-00619-9","url":null,"abstract":"<p><strong>Background: </strong>Complex chromosomal rearrangements (CCRs) are rare chromosomal structural variations, containing a variety of rearrangements such as translocation, inversion and/or insertion. With the development of cytogenetic and molecular genetic techniques, some chromosomal rearrangements that were initially considered to be simple reciprocal translocations in the past might eventually involve more complex chromosomal rearrangements.</p><p><strong>Case presentation: </strong>In this case, a pregnant woman, who had a spontaneous abortion last year, had abnormal prenatal test results again in the second pregnancy. Applying a combination of genetic methods including karyotype analysis, chromosomal microarray analysis, fluorescence in situ hybridization and optical genome mapping confirmed that the pregnant woman was a carrier of a CCR involving three chromosomes and four breakpoints, and the CCR was paternal-origin. Her first and second pregnancy abnormalities were caused by chromosomal microdeletions and microduplications due to the malsegregations of the derivative chromosomes.</p><p><strong>Conclusions: </strong>We presented a rare familial CCR involving three chromosomes and four breakpoints. This study provided precise and detailed information for the subsequent reproductive decision-making and genetic counselling of the patient.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":" ","pages":"41"},"PeriodicalIF":1.3,"publicationDate":"2022-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40373044","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}