Cytogenetic and Genome Research最新文献

{"title":"Large Chromosome 2p Duplication-Associated Mechanisms and Clinical Presentations.","authors":"Xiaolan Fang, Benjamin Hilton, Katie Clarkson, R Curtis Rogers, Richard Schroer, Anna Childers, Wesley G Patterson, Jessica M Davis, David B Everman, Barbara R DuPont","doi":"10.1159/000533218","DOIUrl":"10.1159/000533218","url":null,"abstract":"<p><p>Chromosome 2p (chr2p) duplication, also known as trisomy 2p, is a rare chromosome abnormality associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants (CNVs) in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chr2p as the sole cytogenetic abnormality. In this study, 193 samples at the Greenwood Genetic Center (GGC) with CNVs involving chr2p were evaluated, out of which 86 had chr2p duplications. Among them, 8 patients were identified with large chr2p duplications ranging in size from 9.3 Mb to 89 Mb, and no deletions or duplications involving other chromosomes were identified in those patients. These duplications were associated with inverted duplication, tandem duplication, and duplication as the result of translocation, with no additional CNVs identified by microarray analysis. Confirmation by conventional cytogenetics was performed in 7 of the 8 patients, and the translocations were confirmed by fluorescence in situ hybridization. Interestingly, 1 patient was found to have mosaic complete trisomy 2p as the result of an unbalanced de novo (X;2) chromosomal translocation. X-inactivation was skewed toward the derivative X chromosome, yet it did not appear to extend into the chromosome 2 material. Various shared clinical manifestations were observed in the individuals in this study, including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, and they also have distinct features such as hypotonia, cerebellar hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. In conclusion, single-event large chr2p duplications can result from different mechanisms, including inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p is commonly associated with developmental delay, and additional clinical features may be related to gene dosage effects.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"14-23"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10253107","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":"Effect of Age and Sex on Gene Expression-Based Radiation Biodosimetry Using Mouse Peripheral Blood.","authors":"Constantinos G Broustas, Igor Shuryak, Axel J Duval, Sally A Amundson","doi":"10.1159/000530172","DOIUrl":"10.1159/000530172","url":null,"abstract":"<p><p>Blood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to radiation biodosimetry. However, age and sex could potentially limit the accuracy of the approach. In this study, we determined the impact of age on the peripheral blood cell gene expression profile of female mice exposed to radiation and identified differences and similarities with a previously obtained transcriptomic signature of male mice. Young (2 months) and old (24 months) female mice were irradiated with 4 Gy X-rays, total RNA was isolated from blood 24 hours later and subjected to whole-genome microarray analysis. Dose reconstruction analyses using a gene signature trained on gene expression data from irradiated young male mice showed accurate reconstruction of 0 or 4 Gy doses with root mean square error of ±0.75 Gy (R2 = 0.90) in young female mice. Although dose reconstruction for irradiated old female mice was less accurate than young female mice, the deviation from the actual radiation dose was not statistically significant. Pathway analysis of differentially expressed genes revealed that after irradiation, apoptosis-related functions were overrepresented, whereas functions related to quantities of various immune cell subtypes were underrepresented, among differentially expressed genes from young female mice, but not older animals. Furthermore, young mice significantly upregulated genes involved in phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. Both functions were also overrepresented in young, but not old, male mice following 4 Gy X-irradiation. Lastly, functions associated with neutrophil activation that is essential for killing invading pathogens and regulating the inflammatory response were predicted to be uniquely enriched in young but not old female mice. This work supports the concept that peripheral blood gene expression profiles can be identified in mice that accurately predict physical radiation dose exposure irrespective of age and sex.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"197-209"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117105","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":"Application of the Cytokinesis-Block Micronucleus Assay for High-Dose Exposures Using Imaging Flow Cytometry.","authors":"Lindsay A Beaton-Green, Jessica M Mayenburg, Leonora Marro, Eman M Hassan, Sarita Cuadros Sanchez, Riham Darwish, Sylvie Lachapelle, Nadine Adam, Julie J Burtt, Cyndi Van Den Hanenberg, Matthew A Rodrigues, Qi Wang, David J Brenner, Helen C Turner, Ruth C Wilkins","doi":"10.1159/000532124","DOIUrl":"10.1159/000532124","url":null,"abstract":"<p><p>The cytokinesis-block micronucleus assay is a well-established method to assess radiation-induced genetic damage in human cells. This assay has been adapted to imaging flow cytometry (IFC), allowing automated analysis of many cells, and eliminating the need to create microscope slides. Furthermore, to improve the efficiency of assay performance, a small-volume method previously developed was employed. Irradiated human blood samples were cultured, stained, and analyzed by IFC to produce images of the cells. Samples were run using both manual and 96-well plate automated acquisition. Multiple parameter-based image features were collected for each sample, and the results were compared to confirm that these acquisition methods are functionally identical. This paper details the multi-parametric analysis developed and the resulting calibration curves up to 10 Gy. The calibration curves were created using a quadratic random coefficient model with Poisson errors, as well as a logistic discriminant function. The curves were then validated with blinded, irradiated samples, using relative bias and relative mean square error. Overall, the accuracy of the dose estimates was adequate for triage dosimetry (within 1 Gy of the true dose) over 90% of the time for lower doses and about half the time for higher doses, with the lowest success rate between 5 and 6 Gy where the calibration curve reached its peak and there was the smallest change in MN/BNC with dose. This work describes the application of a novel multi-parametric analysis that fits the calibration curves and allows dose estimates up to 10 Gy, which were previously limited to 4 Gy. Furthermore, it demonstrates that the results from samples acquired manually and with the autosampler are functionally similar.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"131-142"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974697","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":"Radiation-Induced Gene Expression Changes Used for Biodosimetry and Clinical Outcome Prediction: Challenges and Promises.","authors":"Michael Abend, Patrick Ostheim, Matthias Port","doi":"10.1159/000530947","DOIUrl":"10.1159/000530947","url":null,"abstract":"<p><p>As the war in Ukraine progresses, the radiological and nuclear threat has never been as real as now. The formation of life-threatening acute radiation syndrome (ARS), in particular after the deployment of a nuclear weapon or an attack on a nuclear power station, must be considered realistic. ARS is caused by massive cell death, leading to functional organ deficits and, via systemic inflammatory responses, finally aggravates into multiple organ failure. As a deterministic effect, the severity of the disease dictates the clinical outcome. Hence, predicting ARS severity via biodosimetry or alternative approaches appears straightforward. Because the disease occurs delayed, therapy starting as early as possible has the most significant benefit. A clinically relevant diagnosis should be carried out within the diagnostic time window of about 3 days after exposure. Biodosimetry assays providing retrospective dose estimations within this time frame will support medical management decision-making. However, how closely can dose estimates be associated with the later developing ARS severity degrees when considering dose as one among other determinants of radiation exposure and cell death? From a clinical/triage point of view, ARS severity degrees can be further aggregated into unexposed, weakly diseased (no acute health effects expected), and strongly diseased patient groups, with the latter requiring hospitalization as well as an early and intensive treatment. Radiation-induced gene expression (GE) changes occur early after exposure and can be quickly quantified. GE can be used for biodosimetry purposes. Can GE be used to predict later developing ARS severity degrees and allocate individuals to the three clinically relevant groups as well?</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"223-230"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9515121","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":"The Types and Frequencies of X Chromosome Abnormalities in Women with Reproductive Problems.","authors":"Elisavet Kouvidi, Haralambia Tsarouha, Sophia Zachaki, Christina Katsidi, Hara Tsimela, Amelia Pantou, Emmanuel Kanavakis, Ariadni Mavrou","doi":"10.1159/000534428","DOIUrl":"10.1159/000534428","url":null,"abstract":"<p><strong>Introduction: </strong>X chromosome architecture and integrity are essential for normal ovarian function. Both numerical and structural X chromosome abnormalities play an important role in female infertility. This study aimed to determine the types and frequency of X chromosome aberrations detected in women referred for cytogenetic investigation due to reproductive problems.</p><p><strong>Methods: </strong>2,936 women (average age: 37.5 years) were enrolled in the present study. Peripheral blood karyotyping was performed by conventional cytogenetic techniques. For each woman, 20 G-banded metaphases were studied and in case of suspected mosaicism, analysis was extended to 100 metaphases.</p><p><strong>Results: </strong>2,588/2,936 (88.15%) of women had a normal karyotype (46,XX), while 348/2,936 (11.85%) had an abnormal one. Thirty-two women (1.09%) carried autosomal chromosome abnormalities and 316 (10.76%) had X chromosome rearrangements. In 311/2,936 women (10.59%), X chromosome numerical aberrations were detected (low-level mosaicism), and in 5/2,936 cases (0.17%), X structural abnormalities (two with pericentric inversion, one with Xq deletion and two 45,X mosaics, one with an Xp deletion cell line and the other with isochromosome Xq cell line). Low-level X mosaicism was a common finding in women &gt;35 years as compared to younger ones (92.93% vs. 7.07%), a finding consistent with loss of chromosome X with aging. Other X chromosome abnormalities were detected in younger women (32.3 ± 4.13 vs. 41.04 ± 4.5 years). The mean age of women with Turner-like phenotype was 28.75 ± 6.6 years.</p><p><strong>Conclusion: </strong>The study confirms that the incidence of X chromosome abnormalities is increased in women with fertility problems and that karyotype is the gold standard for their identification. Genetic counseling is recommended in these cases to provide information concerning available treatment and fertility options.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"274-278"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101987","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":"Sex as a Factor in Murine Radiation Research: Implications for Countermeasure Development.","authors":"Gregory P Holmes-Hampton, Vidya P Kumar, Kaylee Valenzia, Sanchita P Ghosh","doi":"10.1159/000531630","DOIUrl":"10.1159/000531630","url":null,"abstract":"<p><p>There is an increased threat of exposure to ionizing radiation; in the event of such exposure, the availability of medical countermeasures will be vital to ensure the protection of the population. Effective countermeasures should be efficacious across a varied population and most importantly amongst both males and females. Radiation research must be conducted in animal models which act as a surrogate for the human response. Here, we identify differences in survival in male and female C57BL/6 in both a total body irradiation (TBI) model using the Armed Forces Radiobiology Research Institute (AFRRI) 60Co source and a partial body irradiation (PBI) model using the AFRRI Linear Accelerator (LINAC) with 4 MV photons and 2.5% bone marrow shielding. In both models, we observed a higher degree of radioresistance in female animals and a corresponding radiosensitivity in males. One striking difference in male and female rodents is body size/weight and we investigated the role of pre-irradiation body weight on survivability for animals irradiated at the same dose of irradiation (8 Gy TBI, 14 Gy PBI). We found that weight does not influence survival in the TBI model and that heavier males but lighter females have increased survival in the PBI model. This incongruence in survival amongst the sexes should be taken into consideration in the course of developing radiation countermeasures for response to a mass casualty incident.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"187-196"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677283","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":"Identification of a New Enhancer That Promotes Sox9 Expression by a Comparative Analysis of Mouse and Sry-Deficient Amami Spiny Rat.","authors":"Yurie Hirata, Shusei Mizushima, Shoichiro Mitsukawa, Masafumi Kon, Yoko Kuroki, Takamichi Jogahara, Nobuo Shinohara, Asato Kuroiwa","doi":"10.1159/000536408","DOIUrl":"10.1159/000536408","url":null,"abstract":"<p><strong>Introduction: </strong>Testis differentiation is initiated by the SRY gene on the Y chromosome in mammalian species. However, the Amami spiny rat, Tokudaia osimensis, lacks both the Y chromosome and the Sry gene and acquired a unique Sox9 regulatory mechanism via a male-specific duplication upstream of Sox9, without Sry. In general mammalian species, the SRY protein binds to a testis-specific enhancer to promote SOX9 gene expression. Several enhancers located upstream of Sox9/SOX9 have been reported in mice and humans. In particular, the binding of SRY to the highly conserved enhancer Enh13 is thought to be a common mechanism underlying testis differentiation and sex determination in mammals.</p><p><strong>Methods: </strong>Sequences of T. osimensis homologues of three Sox9 enhancers that were previously reported in mice, Enh8, Enh14, and Enh13, were determined. We performed in vitro assays to confirm enhancer activity involved in Sox9 regulation in T. osimensis.</p><p><strong>Results: </strong>T. osimensis Enh13 showed enhancer activity when co-transfected with NR5A1 and SOX9. Mouse Enh13 was activated by NR5A1 and SRY; however, T. osimensis Enh13 did not respond to SRY, even though the binding sites of SRY and NR5A1 were conserved. To identify the key sequence that is present in mouse but absent from T. osimensis, we performed reporter gene assays using vectors in which partial sequences of T. osimensis Enh13 were replaced with mouse sequences. For T. osimensis Enh13 in which the second half (approximately 430 bp) was replaced with the corresponding mouse sequence, activity in response to NR5A1 and SRY was recovered. Further, reporter assays revealed that multiple regions in the second half of the mouse Enh13 sequence are required for the response to NR5A1 and SRY. The latter 49 bp was particularly important and contained four binding sites for three transcription factors, POU2F1, HOXA3, and GATA1.</p><p><strong>Conclusion: </strong>We showed that there are unknown sequences responsible for the interaction between NR5A1 and SRY and mEnh13 based on comparative analyses of Sry-dependent and Sry-independent species. Our comparative analyses revealed new molecular mechanisms underlying mammalian sex determination.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"307-316"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511974","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":"Candidate Gene Expression in Regional Population and Its Relevance for Radiation Triage.","authors":"Nandhini Kannan, Teena Koshy, Venkateswarlu Raavi, Emmanuel Bhaskar, Swathy Moorthy, Venkata Sai Pulivadula Mohanarangam, Satish Srinivas Kondaveeti, Shangamithra Visweswaran, Venkatachalam Perumal","doi":"10.1159/000531258","DOIUrl":"10.1159/000531258","url":null,"abstract":"<p><p>Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p &lt; 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"210-222"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9600636","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":"Genome Mapping Nomenclature.","authors":"Sarah Moore, Jean McGowan-Jordan, Adam C Smith, Katrina Rack, Udo Koehler, Marian Stevens-Kroef, Hayk Barseghyan, Rashmi Kanagal-Shamanna, Ros Hastings","doi":"10.1159/000535684","DOIUrl":"10.1159/000535684","url":null,"abstract":"<p><strong>Background: </strong>Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation and have application in constitutional genetic disorders, hematological neoplasms, and solid tumors. Genome mapping can detect balanced and unbalanced structural variation, copy number changes, and haplotypes. The technique is analogous to chromosomal microarray analysis, although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities in a single assay than array, karyotyping, or FISH alone.</p><p><strong>Key messages: </strong>This paper describes a specific nomenclature for genome mapping that can be used by diagnostic and research centers to report their findings accurately. An international nomenclature is essential for patient results to be understood by different healthcare providers as well as for clear communication in publications and consistency in databases.</p><p><strong>Summary: </strong>Genome mapping can detect aneuploidy, balanced and unbalanced structural variation, as well as copy number changes. The Standing Committee for the International System for Human Cytogenomic Nomenclature (ISCN) recognised there was a need for a specific nomenclature for genome mapping that encompasses the range of abnormalities detected by this technique. This paper explains the general principles of the nomenclature as well as giving specific ISCN examples for the different types of numerical and structural rearrangements.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"236-246"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800748","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":"Expanding the Clinical and Molecular Spectrum of FOXG1- and ZBTB18-Associated Neurodevelopmental Disorders.","authors":"Alejandro J Brea-Fernández, Federica A Souto-Trinei, Elba Iglesias, Pilar Caamaño, Berta Rodríguez Sánchez, Carmen Gómez Lado, Jesús Eiris, Montse Fernández-Prieto, Francisco Barros, Roberto J Brea, Ángel Carracedo","doi":"10.1159/000535660","DOIUrl":"10.1159/000535660","url":null,"abstract":"<p><strong>Introduction: </strong>The zinc finger BTB domain-containing protein ZBTB18 binds to FOXG1 to form a transcriptional repressive complex involved in neuronal differentiation. Disruption of the components of this complex results in chromosome 1q43-q44 deletion syndrome/intellectual developmental disorder 22 or in FOXG1 syndrome.</p><p><strong>Case presentation: </strong>This study reports on five patients with cognitive and behavioral impairment, seizures, microcephaly, and/or congenital brain abnormalities. Whole-exome sequencing identified deleterious ZBTB18 variants in three patients and deleterious FOXG1 variants in the remaining patients. We have detected a missense variant within the BTB domain of ZBTB18 in two affected monozygotic twins. In addition, we observed agenesis of the septum pellucidum in a missense FOXG1 carrier with a severe FOXG1 syndrome.</p><p><strong>Conclusion: </strong>Although the ZBTB18 zinc finger domains harbor the majority of known deleterious variants, we report a novel de novo rare missense variant within the BTB domain. The agenesis of the septum pellucidum observed in a missense FOXG1 carrier could be considered as a novel clinical feature associated with FOXG1 syndrome. The severe FOXG1 syndrome in this patient contrasts with the milder phenotype expected for a missense. Genetic or environmental factors may explain this phenotypic variability in FOXG1 syndrome.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"301-306"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498011","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}