Normal Karyotype Research Articles

The Transcriptomic and Gene Fusion Landscape of Pleomorphic Salivary Gland Adenomas.

Pleomorphic adenoma (PA) is the most common salivary gland tumor. PAs are characterized by chromosomal rearrangements of 8q12 and 12q14-15, leading to gene fusions involving the PLAG1 and HMGA2 oncogenes. Here, we performed the first comprehensive study of the transcriptomic and gene fusion landscape of 38 cytogenetically characterized PAs. RNA-seq identified PLAG1 or HMGA2 fusions in 33/38 cases (87%), of which 15 were novel fusions. Fusions were found also in tumors with normal karyotype, demonstrating that they are generated by cryptic rearrangements. PLAG1 was mainly activated by promoter swapping and HMGA2 by truncation of its 3'-part. RNA-seq revealed upregulation of genes involved in extracellular matrix production, WNT-signaling, and epithelial-mesenchymal transition in PA compared to normal salivary tissue. Principal component analysis identified two PA subclusters characterized by PLAG1- and HMGA2-activation, respectively, that differed in expression of genes involved in the immune system, cell adhesion, and microenvironment remodeling. Moreover, comparative analyses of PA and salivary carcinomas revealed that PA resembles myoepithelial carcinoma. Our study reveals new oncogenic gene fusions and expands our knowledge about the molecular underpinnings of PA.

A human induced pluripotent stem cell line, NIMHi016-A, established from fibroblasts of a neuromuscular disease patient carrying PGK1/p. Asn5Lys variant.

PGK1 (phosphoglycerate kinase-1) is required for ATP production in the body. Mutation in the PGK1 gene causes a rare, inherited metabolic disorder causing deficiency of enzyme PGK1, leading to hemolytic anemia, neurological symptoms, and muscle weakness. We generated induced pluripotent stem cells (iPSCs) from a patient carrying a PGK1 variant by isolating fibroblasts from skin punch biopsy and reprogramming using CytoTune iPS 2.0 Sendai reprogramming kit. The resulting iPSCs had normal karyotype, expressed pluripotent markers, and differentiated into three germ layers in vitro. The iPSC line NIMHi016-A can be used to model neuromuscular disorders.

Establishing of human induced pluripotent stem cell line DMSCi002-A from the hematopoietic stem cells of a healthy male donor.

Using the integration-free episomal vector containing the reprogramming components OCT3/4/shp53, Sox2/KLF4, L-MYC/LIN28, and EBNA-1, hematopoietic stem cells obtained from a healthy 33-year-old man were effectively reprogrammed and turned into induced pluripotent stem cells (iPSCs). The reprogrammed iPSCs were grown without the use of feeders. They exhibited a normal karyotype, displayed pluripotency markers, and differentiated into cells from the three germ layers. This DMSCi002-A line may serve as a control for investigating disease mechanisms.

Analysis of gene expression difference and biological process in chorionic villi of unexplained recurrent spontaneous abortion

ObjectiveTo explore the biological relationship between the regulatory signal pathways involved in differentially expressed genes and recurrent spontaneous abortion (RSA) by analyzing the gene expression microarray data of unexplained RSA.MethodsThe gene expression profile data of chorionic villi from unexplained recurrent abortion with normal karyotype and selective induced abortion were compared. Differentially expressed genes were analyzed by the “Limma” package in R Studio, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out with “Cluster Profiler” and “org.hs.eg.db” packages. Finally, hub genes were identified through constructing the protein-protein interaction (PPI) network from the differentially expressed gene dataset in the STRING database. And the hub genes were verified by RT-PCR. The expression of TH1 and TH2 cytokines representing IL-2, IL-10 and their receptors related to hub gene immune regulation were detected by enzyme-linked immunosorbent assay (ELISA) and western blot (WB), respectively.ResultsA total of 295 differentially expressed genes were identified in the dataset GSE22490, with a significance level of P < 0.05 and an absolute log-fold change > 1.0, which included 166 up-regulated genes and 129 down-regulated genes. Go and KEGG enrichment analysis of these differentially expressed genes (P < 0.05,FDR < 0.05) revealed significant involvement in the regulation of inflammatory and immune responses. The PPI analysis revealed that the hub genes FCGR3A, TLR2, BTK, CLEC7A and CD163 were centrally located in the network cluster which were composed of the proteins encoded by differentially expressed genes associated with RSA. The mRNA levels of FCGR3A, TLR2 and CLEC7A in the RSA group were significantly higher than those in the NC group (P < 0.05). The protein expression level of TLR2 was also significantly increased in the RSA group (P < 0.05). The level of IL-2 in the RSA group was significantly higher than that in the NC group (P < 0.05), while the protein expression level of its receptor was not different(P > 0.05). There was no significant difference in the expression levels of IL-10 and its receptor between the two groups (P > 0.05).ConclusionAbnormal immune response plays an important role in unexplained RSA. The imbalance in immune regulation may be one of the most important reasons behind this phenomenon. These findings provide a foundation for further research into the mechanisms underlying RSA.

Capture primed pluripotency in guinea pig.

Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency. Wingless/Integrated(WNT) signaling inhibition is also essential for their maintenance. GpEpiSCs express key pluripotency markers (OCT4, SOX2, NANOG) and share transcriptional similarities with human and mouse primed stem cells. While many genes are conserved between guinea pig and human primed stem cells, transcriptional analysis also reveals species-specific differences in pluripotency-related pathways. Epigenetic analysis highlights bivalent gene regulation, underscoring their developmental potential. This work demonstrates both the evolutionary conservation and divergence of primed pluripotent stem cells, providing a new tool for biomedical research and enhancing guinea pigs' utility in studying human diseases.

New line of mesenchymal stem cell isolated from warton’s jelly of the umbical cord of male human donor

A new non-immortalized fibroblast-like cell line, named MSCWJ-3, was generated and characterized. Characteristics during long-term cultivation (6–24 passages) confirm the status of MSCs. It is shown: 1) a gradual increase in the proportion of senescent cells during long-term cultivation; 2) a significant decrease in the proliferation index by the 24th passage; 3) preservation of the normal diploid karyotype of the man (46, XY) during the entire period of cultivation, trisomy for different autosomes in single cells, absence of structural chromosomal rearrangements; 4) a high proportion of cells carrying surface antigens characteristic of MSCs: CD44, CD73, CD90, CD105, HLA-ABC and a low proportion with antigens CD34, CD45 and HLA-DR over 24 passages. Cells of the MSCWJ-3 line are capable of differentiation in the osteogenic and adipogenic directions at early and late passages; differentiation in the chondrogenic direction is absent. In general, there are some differences with previously obtained lines isolated from the same source and are associated mainly with the degree of expression of a number of status characteristics.

Preimplantation genetic testing for structural rearrangements by genome-wide SNP genotyping and haplotype analysis: a prospective multicenter clinical study.

Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) has been widely utilized to select euploid embryos in patients carrying balanced chromosomal rearrangements (BCRs) by chromosome copy number analysis. However, reliable and extensively validated PGT-SR methods for selecting embryos without BCRs in large-cohort studies are lacking. In this prospective, multicenter, cohort study, carriers with BCRs undergoing PGT-SR were recruited across 12 academic fertility centers within China. PGT-SR was performed using genome-wide SNP genotyping and haplotyping approach. Parental haplotypes were phased by available genotypes from a close relative or an unbalanced embryo. The karyotypes of embryos were inferred from the haplotypes. Only a single embryo was transferred in each cycle. Between April 2018 and March 2023, 1298 carriers we randomly enrolled. A total of 7867 blastocysts from 1603 PGT-SR cycles were biopsied, in which 7750 (98.51%) were successfully genotyped and analyzed. Overall, 75.98% (1218/1603) of cycles obtained euploid embryos and 53.15% (852/1603) generated non-carrier embryos. The proportion of carrier and non-carrier embryos was similar in different subgroups. A total of 1030 non-carrier and 439 carrier embryos were transferred, 817 healthy babies were delivered cumulatively. Our results demonstrate that SNP-haplotyping method is highly accurate (sensitivity 95% CI: 98.34%-100%, specificity 95% CI: 96.63%-100%, respectively), and can be applied universally to different BCR types. Moreover, the clinical outcomes were comparable between the carrier and non-carrier embryo groups. This study demonstrates the effectiveness of preimplantation genetic genome-wide SNP-genotyping and haplotyping method, resulting in the delivery of more babies with a normal karyotype. This study was funded by the National Key Research and Development Program of China (2022YFC2703200, 2021YFC2700600, 2021YFC2700500), National Natural Science Foundation of China (82201807, 82171639, 82071717). Shanghai Science and Technology Innovation Action Plan Program (18411953800), and the Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2022YQ075).

Detection of KMT2A Partial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes.

KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal (n = 21) or non-complex (n = 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, with FLT3 ITD and DNMT3A prevalent in AML and DNMT3A and RUNX1 common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detecting KMT2A PTD. Neoplasms with KMT2A PTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients with KMT2A PTD are generally refractory to conventional therapy, except for de novo AML.

Prevalence and comparative analysis of Y chromosome microdeletions in recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is defined as the spontaneous loss of two or more pregnancies before reaching viability. Diagnosis for couples with RPL usually involves only the female partner. However, it is seen that male partners contribute equally to the occurrence of spontaneous abortions as the Y chromosome harbors several genes that control spermatogenesis and the quality of sperms. Three non-overlapping regions (AZFa, AZFb, AZFc) in the distal half of Y chromosome have been reported to be associated with spermatogenesis in males with normal karyotype. Microdeletions in these three regions have been identified in many male partners with repeated abortions. The STS regions of the Y chromosome are prone to self-recombination, making it susceptible to deletions, thereby leading to poor sperm quality and fetal implantation failure. The present study aimed to identify the frequency and type of microdeletions among male partners of RPL women. Analysis revealed nearly 76% of cases revealed microdeletions, whereas no deletions were observed among controls in Y chromosome, suggesting a strong link between RPL and microdeletion in the AZF regions of the Y chromosome in the male partner.

Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function.

Complex aneuploidy triggers autophagy and p53-mediated apoptosis and impairs the second lineage segregation in human preimplantation embryos

About 70% of human cleavage stage embryos show chromosomal mosaicism, falling to 20% in blastocysts. Chromosomally mosaic human blastocysts can implant and lead to healthy new-borns with normal karyotypes. Studies in mouse embryos and human gastruloids showed that aneuploid cells are eliminated from the epiblast by p53-mediated apoptosis while being tolerated in the trophectoderm. These observations suggest a selective loss of aneuploid cells from human embryos, but the underlying mechanisms are not yet fully understood. Here, we investigated the cellular consequences of aneuploidy in a total of 125 human blastocysts. RNA-sequencing of trophectoderm cells showed activated p53 pathway and apoptosis proportionate to the level of chromosomal imbalance. Immunostaining corroborated that aneuploidy triggers proteotoxic stress, autophagy, p53-signaling, and apoptosis independent from DNA damage. Total cell numbers were lower in aneuploid embryos, due to a decline both in trophectoderm and in epiblast/primitive endoderm cell numbers. While lower cell numbers in trophectoderm may be attributed to apoptosis, aneuploidy impaired the second lineage segregation, particularly primitive endoderm formation. This might be reinforced by retention of NANOG. Our findings might explain why fully aneuploid embryos fail to further develop and we hypothesize that the same mechanisms lead to the removal of aneuploid cells from mosaic embryos.

Complex aneuploidy triggers autophagy and p53-mediated apoptosis and impairs the second lineage segregation in human preimplantation embryos.

About 70% of human cleavage stage embryos show chromosomal mosaicism, falling to 20% in blastocysts. Chromosomally mosaic human blastocysts can implant and lead to healthy new-borns with normal karyotypes. Studies in mouse embryos and human gastruloids showed that aneuploid cells are eliminated from the epiblast by p53-mediated apoptosis while being tolerated in the trophectoderm. These observations suggest a selective loss of aneuploid cells from human embryos, but the underlying mechanisms are not yet fully understood. Here, we investigated the cellular consequences of aneuploidy in a total of 125 human blastocysts. RNA-sequencing of trophectoderm cells showed activated p53 pathway and apoptosis proportionate to the level of chromosomal imbalance. Immunostaining corroborated that aneuploidy triggers proteotoxic stress, autophagy, p53-signaling, and apoptosis independent from DNA damage. Total cell numbers were lower in aneuploid embryos, due to a decline both in trophectoderm and in epiblast/primitive endoderm cell numbers. While lower cell numbers in trophectoderm may be attributed to apoptosis, aneuploidy impaired the second lineage segregation, particularly primitive endoderm formation. This might be reinforced by retention of NANOG. Our findings might explain why fully aneuploid embryos fail to further develop and we hypothesize that the same mechanisms lead to the removal of aneuploid cells from mosaic embryos.

Survival impact of hypoxia-inducible factor-1 alpha (HIF-1α) in Nucleophosmin1 mutated acute myeloid leukemia.

Nucleophosmin1 (NPM1) mutated acute myeloid leukemia (AML) without FLT3-ITD mutation is classified as a favorable risk AML which responds well to cytarabine therapy. Hypoxia-inducible factor-1 alpha (HIF-1α) promotes leukemic cell survival and maintains leukemic stem cell quiescence possibly contributing to cytarabine resistance. This study evaluated HIF-1α expression using immunohistochemistry in bone marrow of 29 newly diagnosed NPM1+FLT3-ITD- normal karyotype AML patients and analyzed its correlation with survival. All patients achieved complete remission after standard induction chemotherapy and proceeded to cytarabine consolidations. Positive HIF-1α staining with golgi body pattern and strong cytoplasmic HIF-1α expression was identified in 34.5% and 58.6% of patients, respectively. The expression of golgi body or strong cytoplasmic HIF-1α expression was related to increased relapse (p = 0.048) with significantly inferior relapse-free survival (RFS, p = 0.042). Using multivariate analysis, extramedullary disease at diagnosis was revealed as an independent prognostic factor for adverse RFS (hazard ratio [HR] 3.82; 95% confidence interval [CI] 1.26-11.55, p = 0.018), while golgi body or strong cytoplasmic HIF-1α expression showed a trend toward poor RFS (HR 3.56; 95% CI 1.00-12.69, p = 0.050). In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in NPM1+FLT3-ITD- AML. Further studies with the large number of patients are warranted.

Mutation Analysis of ASXL1 in Normal Karyotype Myelodysplastic Syndromes: Experience From Pakistan

ABSTRACTBackgroundThe challenges in advancing treatment modalities for myelodysplastic syndromes (MDS) may stem from an incomplete understanding of the disease's complex pathophysiology and lack of reliable prognostic molecular markers. Advanced genomic techniques have revolutionized disease prognosis and risk stratification, particularly for cases with a normal karyotype.AimThe present study aimed to analyze ASXL1 mutations in MDS exhibiting a normal karyotype.Methods and ResultsThe study enrolled 41 MDS patients with normal karyotypes. Genomic DNA was extracted from peripheral blood samples, followed by Sanger sequencing. The Chi‐square and Mann–Whitney U tests were applied to assess the association of age and hemogram with the occurrence of mutations. Survival analysis was done via the Kaplan–Meier method. Statistical operations were performed employing the IBM SPSS Statistics version 24. The patients had a median age of 40 years comprising 28 (68.3%) males and 13 (31.7%) females. ASXL1 mutations were identified in 8 (19.5%), particularly stopgain single nucleotide variant (SNV) and frameshift insertion. The median total leucocyte count × 109/L and blast percentage among the patients with ASXL1 mutation were 3.9 and 4.5, respectively. A survival of 85 weeks was recorded for ASXL1‐mutated and nonmutated cases. The association of ASXL1 mutation status with age and studied hematological parameters was found nonsignificant.ConclusionASXL1 mutation plays a pivotal role in MDS prognosis, warranting assessment at diagnosis for risk stratification and treatment decisions. Early identification of ASXL1 mutation, particularly in low‐risk patients or those with normal karyotype, is imminent to identify patients exhibiting unfavorable prognosis. Integrating molecular insights into existing risk assessment holds significance for improved clinical outcomes, reduction in disease progression, and ultimately the improved quality of life and should be identified early in the course of disease even in the developing world.

Generation of a PDK-1 knockout human embryonic stem cell line by CRISPR/(WAe009-A-2K) Cas9 editing.

Pyruvate Dehydrogenase Kinase1 (PDK1) belongs to the family of kinases, regulates diverse metabolic processes. PDK1 is a susceptibility locus for heart failure via thinning of ventricle walls, and enlarged atria and ventricles. We successfully developed a PDK1 knockout (PDK1-/-) human embryonic stem cell (hESC) line using an episomal vector-based CRISPR/Cas9 system explore the role of PDK in human heart development. This PDK1-KO hESC line-maintained stem cell-like morphology, pluripotency, and normal karyotype and can differentiate into all three germ layers in vivo. This cell line will be a valuable tool for future research on the role of PDK1 in heart development.

Human induced pluripotent stem cell line (PNUSCRi005-A) generated from severe type of Hunter syndrome patient carrying exonic deletion (exon 4-7 del) in in human iduronate 2-sulfatase gene.

Mucopolysaccharidosis Type Ⅱ, as Known as Hunter syndrome, is a rare X-liked genetic disease caused by mutations in iduronate-2-sulfatase (IDS) gene. We obtained peripheral blood mononuclear cells (PBMCs) from a patient with a severe type of Hunter syndrome carrying c.418+495_1006+1304 deletion in the IDS gene. We generated an induced pluripotent stem cell (iPSC) line (PNUSCRi005-A hiPSCs) from the PBMCs of the patient using non-integrative Sendai virus. The hiPSCs exhibited embryonic stem cell-like characteristics, showed differentiation properties into three germ layers, and had a normal karyotype.

The Clinical Impact of NPM1 Mutations and the Effect of Concurrent Mutations in Acute Myeloid Leukemia: Unraveling the Prognostic Significance.

Nucleophosmin (NPM1) gene mutations occur in approximately 30%-35% of individuals with an initial diagnosis of acute myeloid leukemia (AML). Mutations in this gene have been reported in 50%-60% of AML patients with a normal karyotype. These mutations help to distinguish clinicopathological and molecular features, setting them apart as a unique subset within the heterogeneous landscape of AML. In the present study, we investigated the frequency and clinical impact of NPM1 mut in 100 newly diagnosed adult Syrian patients with AML-normal karyotype (NK) using direct sequencing. We analyzed 100 AML-NK patients using direct sequencing to assess the prevalence and clinical impact of NPM1 mutations, as well as the co-occurrence of FLT3-ITD and DNMT3A mutations. Our results revealed that the prevalence of NPM1 mut was 22% among the patients; 86.4% of these mutations were type A (NM_002520.5:c.860-863dupTCTG), while 13.6% were de novo mutations (c.863_864insCCTG, p.Trp288CysfsTer12), (c.861_862dup, p.Trp288SerfsTer13), and (c.863_864insCCGG, p.Trp288CysfsTer12). Among our patients, 22% exhibited NPM1 mut, with 7% also harboring FLT3-ITD mut and 2% having DNMT3A mut. The presence of NPM1 mut was correlated with a statistically significant increase in bone marrow blast percentage (p = 0.017). Notably, patients with NPM1 mut displayed significantly higher mortality rates, with 72.7% succumbing to the disease compared to 29.5% of patients without NPM1 mut (p < 0.001). Furthermore, our results showed that when the overall survival (OS) time exceeded 8.35 months, the likelihood of NPM1 wild-type status was greater. The evaluation of NPM1 mut and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.

Generation of a human induced pluripotent stem cell line ZZUNEUi030-A from a female patient carrying a heterozygous CALM2 (c.395 A > T) mutation

Calmodulin mutations can cause life-threatening long QT syndrome involving CALM1, CALM2, and CALM3. In this study, human induced pluripotent stem cells ZZUNEUi030-A were derived from a female patient with heterozygous CALM2 gene c. 395A → T by Sendai virus non-integrated reprogramming technology. The cell line showed a normal female karyotype (46, XX), expressed pluripotency markers, and had the ability to differentiate into three germ layers in vitro. ZZUNEUi030-A can be used as a cell disease model to study the pathogenesis of LQT caused by calmodulin mutations.

Genetic Analysis of 17q Terminal Partial Trisomy.

Chromosomal trisomy syndrome is associated with diverse clinical phenotypes, including intellectual disability. Partial trisomy of the distal 17q is a rare anomaly with similar clinical features, including psychomotor and growth deficits, facial dysmorphism, and microcephaly. Here, we describe three patients from two unrelated families with terminal trisomy 17q. We performed G-banding karyotype and chromosomal microarray analyses. The child in Family 1 had a 31.3 Mb mosaic duplication on chromosome 17. Family 2 comprised dizygotic twins with a 263 kb deletion on chromosome 15 and a 9.2 Mb duplication on chromosome 17; however, normal karyotyping results were obtained for both parents. We also analyzed the genetic mechanisms underlying the occurrence of these chromosomal aberrationsand summarized the literature describing known genotype-phenotype correlations. Given the rarity of partial trisomy of terminal 17q, these cases will provide new insights into the diagnosis of this condition and genotype-phenotype correlations, which can aid in the detection of such conditions and genetic counseling.

Generation of induced pluripotent stem cell line, NIMHi013-A, from PBMCs of a female child with epilepsy carrying a novel SCN1A variant

The iPSC line NIMHi013-A was generated from peripheral blood mononuclear cells of a paediatric patient with drug resistant epilepsy. The proband was found to have a likely pathogenic missense variant in the SCN1A gene in heterozygous state, which segregated in the affected in dominant fashion. The variant is in the Nav1.1 subunit of the voltage gated sodium ion channel. The iPSCs were generated using Sendai virus-based reprogramming. These iPSCs express pluripotent markers, present a normal karyotype and could differentiate into three germ layers. The iPSC line NIMHi013-A can be used to investigate epileptogenesis in vitro