Table1_The Role of Ion Channel-Related Genes in Autism Spectrum Disorder: A Study Using Next-Generation Sequencing.DOCX

The clinical heterogeneity of autism spectrum disorder (ASD) is closely associated with the diversity of genes related to ASD pathogenesis. With their low effect size, it has been hard to define the role of common variants of genes in ASD phenotype. In this study, we reviewed genetic results and clinical scores widely used for ASD diagnosis to investigate the role of genes in ASD phenotype considering their functions in molecular pathways. Genetic data from next-generation sequencing (NGS) were collected from 94 participants with ASD. We analyzed enrichment of cellular processes and gene ontology using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We compared clinical characteristics according to genetic functional characteristics. We found 266 genes containing nonsense, frame shift, missense, and splice site mutations. Results from DAVID revealed significant enrichment for “ion channel” with an enrichment score of 8.84. Moreover, ASD participants carrying mutations in ion channel-related genes showed higher total IQ (p = 0.013) and lower repetitive, restricted behavior (RRB)-related scores (p = 0.003) and mannerism subscale of social responsiveness scale scores, compared to other participants. Individuals with variants in ion channel genes showed lower RRB scores, suggesting that ion channel genes might be relatively less associated with RRB pathogenesis. These results contribute to understanding of the role of common variants in ASD and could be important in the development of precision medicine of ASD.</p

Table_1_Unraveling trajectories from aplastic anemia to hematologic malignancies: genetic and molecular insights.docx

BackgroundAplastic anemia (AA), characterized by hematopoietic stem cell deficiency, can evolve into different hematologic malignancies. Our understanding of the genetic basis and mechanisms of this progression remains limited.MethodsWe retrospectively studied 9 acquired AA patients who later developed hematologic malignancies. Data encompassed clinical, laboratory, karyotype, and next-generation sequencing (NGS) information. We explored chromosomal alterations and mutation profiles to uncover genetic changes underlying the transition.ResultsNine AA patients developed myelodysplastic syndrome (seven patients), acute myeloid leukemia (one patient), or chronic myelomonocytic leukemia (one patient). Among eight patients with karyotype results at secondary malignancy diagnosis, monosomy 7 was detected in three. Trisomy 1, der(1;7), del(6q), trisomy 8, and del(12p) were detected in one patient each. Among three patients with NGS results at secondary malignancy diagnosis, KMT2C mutation was detected in two patients. Acquisition of a PTPN11 mutation was observed in one patient who underwent follow-up NGS testing during progression from chronic myelomonocytic leukemia to acute myeloid leukemia.ConclusionThis study highlights the genetic dynamics in the progression from AA to hematologic malignancy. Monosomy 7’s prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression.</p

Datasheet1_Analysis of trio test in neurodevelopmental disorders.pdf

BackgroundTrio test has been widely used for diagnosis of various hereditary disorders. We aimed to investigate the contribution of trio test in genetically diagnosing neurodevelopmental disorders (NDD).MethodsWe retrospectively reviewed 2,059 NDD cases with genetic test results. The trio test was conducted in 563 cases. Clinical usefulness, optimal timing, and methods for the trio test were reviewed.ResultsPathogenic or likely pathogenic variants were detected in 112 of 563 (19.9%) patients who underwent the trio test. With trio test results, the overall diagnostic yield increased by 5.4% (112/2,059). Of 165 de novo variants detected, 149 were pathogenic and we detected 85 novel pathogenic variants. Pathogenic, de novo variants were frequently detected in CDKL5, ATP1A3, and STXBP1.ConclusionThe trio test is an efficient method for genetically diagnosing NDD. We identified specific situations where a certain trio test is more appropriate, thereby providing a guide for clinicians when confronted with variants of unknown significance of specific genes.</p

Additional file 1 of Optical genome mapping identifies clinically relevant genomic rearrangements in prostate cancer biopsy sample

Additional file 1: Fig. S1. Inter/Intra-chromosomal translocations

Additional file 2 of Optical genome mapping identifies clinically relevant genomic rearrangements in prostate cancer biopsy sample

Additional file 2: Table S1. Genome mapping summary. Table S2. All non-masked CNVs called by Bionano Analysis Pipeline. Table S3. All SVs called by Bionano Analysis Pipeline

Table_1_Genetic diagnosis of inborn errors of immunity using clinical exome sequencing.xlsx

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA1. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments.</p

Table_1_Feasibility and clinical applicability of genomic profiling based on cervical smear samples in patients with endometrial cancer.docx

PurposeCervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients.Materials and methodsPreoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes.ResultsCervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer.ConclusionCervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.</p

Image_1_Feasibility and clinical applicability of genomic profiling based on cervical smear samples in patients with endometrial cancer.jpeg

PurposeCervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients.Materials and methodsPreoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes.ResultsCervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer.ConclusionCervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.</p

Image_2_Feasibility and clinical applicability of genomic profiling based on cervical smear samples in patients with endometrial cancer.jpeg

PurposeCervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients.Materials and methodsPreoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes.ResultsCervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer.ConclusionCervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.</p

Image_3_Feasibility and clinical applicability of genomic profiling based on cervical smear samples in patients with endometrial cancer.jpeg

PurposeCervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients.Materials and methodsPreoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes.ResultsCervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer.ConclusionCervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.</p