Cytogenetic and Genome Research最新文献

{"title":"Quality Gaps in Cytogenetic Reporting: A Single-Center Retrospective Audit of 225 Bone Marrow Karyotype Reports in Hematologic Malignancies.","authors":"Lamia Alsubaie, Sarah Alsobaie, Nawaf Alhammad, Luluh Aldhubayi, Yazeed Al-Sheikh","doi":"10.1159/cgr/achag009","DOIUrl":"https://doi.org/10.1159/cgr/achag009","url":null,"abstract":"<p><strong>Introduction: </strong>Cytogenetic findings are essential for diagnosis and prognostic risk stratification in hematologic malignancies. However, the extent to which routine karyotype reports incorporate clinically relevant interpretation remains variable. This study evaluated the completeness, accuracy, and clinical integration of cytogenetic reporting.</p><p><strong>Methods: </strong>We retrospectively reviewed 225 consecutive bone marrow karyotype reports issued between October 2020 and July 2024 from a tertiary-care cytogenetics laboratory. Reports were assessed for interpretive commentary, disease-specific risk stratification, actionable testing recommendations, genetic counseling referral, turnaround time (TAT), and ISCN accuracy. Risk stratification analyses were restricted to cases eligible for established disease-specific frameworks (107/225; 47.6%).</p><p><strong>Results: </strong>ISCN errors were identified in 72/225 reports (32.0%), most commonly involving bracketing and subclone notation. Explicit risk-tier documentation was present in only 3/225 reports (1.33%). Among AML cases with documented risk assessment, misclassification occurred in 3/15 cases (20.0%), whereas no misclassification was observed in MDS. Actionable testing recommendations were documented in 5/225 reports (2.22%), and 4/225 reports (1.78%) contained ISCN results without interpretive narrative. Genetic counseling recommendations were absent from all reports, including four cases meeting predefined criteria. Median TAT was 30.5 days (IQR 23-44; 90th percentile 72.3 days), exceeding recommended benchmarks.</p><p><strong>Conclusions: </strong>Cytogenetic reporting gaps primarily reflect limited clinical interpretation rather than technical reporting deficiencies. Standardized diagnosis-aware templates and quality monitoring may improve reporting completeness, consistency, and clinical utility.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180066","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":"A novel microdeletion syndrome involving 17q23.3 region in a child with short stature and multiple congenital anomalies: A Case Report.","authors":"Peter Ivan Hadiprajitno, Tri Indah Winarni, Nani Maharani, Agustini Utari, Nydia Rena Benita Sihombing","doi":"10.1159/cgr/achag011","DOIUrl":"https://doi.org/10.1159/cgr/achag011","url":null,"abstract":"<p><p>Microdeletion syndromes are rare chromosomal abnormalities causing diverse clinical features due to gene dosage imbalances. Deletions in chromosome 17q23.3 have been linked to neurodevelopmental and growth disorders, although the genotype-phenotype correlations remain unclear. An eight-month-old male baby presented with short stature, low-set ears, cardiac anomalies, and multiple congenital malformations. He was born via C-section due to intrauterine growth restriction and exhibited craniofacial dysmorphism, lymphatic vessel dysplasia, micropenis, undescended testes, atrial septal defect, and subclinical hypothyroidism. The phenotype raised clinical suspicion of Noonan Syndrome. However, exome sequencing revealed no pathogenic variants in RASopathy-related genes. Copy number variant (CNV) analysis identified a ∼1.5 Mb deletion on chromosome 17q23.3, affecting 30 genes, including TANC2, which serves as the primary breakpoint gene and plays an essential role in synaptic development. This case highlights the role of CNV analysis in patients suspected of having Noonan Syndrome with negative single-gene testing and suggests an expanded phenotypic spectrum associated with 17q23.3 microdeletion.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166085","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":"Three-Way Chromosomal Translocation Involving KMT2A::MLLT3 in AML: A Case Report and Genomic Characterization.","authors":"Yu Jeong Choi, Ho Hyun Song, Jung-Ah Kim, Rojin Park, Byung Ryul Jeon, Seug Yun Yoon, Jieun Kim","doi":"10.1159/cgr/achag010","DOIUrl":"https://doi.org/10.1159/cgr/achag010","url":null,"abstract":"<p><strong>Introduction: </strong>Complex chromosomal translocations can obscure the identification of pathogenic rearrangements involving KMT2A in acute myeloid leukemia (AML).</p><p><strong>Case presentation: </strong>We report a 20-year-old female with AML harboring a novel three-way translocation, t(9;11;19)(p21;q23;q13.1), resulting in a KMT2A::MLLT3 fusion. The patient presented with gingival swelling, oral ulcers, anemia, thrombocytopenia, leukocytosis, and 95% peripheral blasts. Flow cytometry showed blasts expressing CD11c, CD13, CD33, CD38, CD64, CD117, and HLA-DR. Conventional cytogenetics and KMT2A break-apart FISH confirmed rearrangement in nearly all cells. Whole-genome sequencing resolved the structural architecture, identifying a BND-type event fusing KMT2A exon 8 to MLLT3 exon 6, along with a non-functional head-to-head involvement of TBCB. RNA sequencing confirmed the pathogenic KMT2A::MLLT3 transcript without evidence of TBCB fusion or overexpression. Additional NRAS and KRAS mutations were detected. The patient achieved complete remission following induction and consolidation chemotherapy but relapsed one year later. She subsequently underwent allogeneic stem cell transplantation, relapsed four months post-transplant, and died two years after diagnosis.</p><p><strong>Conclusion: </strong>This case represents an exceptionally rare instance of KMT2A::MLLT3 generated through a three-way complex translocation and highlights the utility of whole-genome and transcriptome sequencing in clarifying rearrangement topology. The aggressive clinical course raises important questions about the prognostic implications of structural complexity and cooperating RAS mutations in KMT2A-rearranged AML.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164675","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":"Chromosomal location of repetitive DNA supports the Robertsonian fusion hypothesis in the carpenter ant Camponotus rufipes (Fabricius, 1775).","authors":"Ana Paula Rocha Moraes, Gisele Amaro Teixeira, Luísa Antônia Campos Barros, Hilton Jeferson Alves Cardoso de Aguiar, Denilce Meneses Lopes","doi":"10.1159/cgr/achag006","DOIUrl":"https://doi.org/10.1159/cgr/achag006","url":null,"abstract":"<p><strong>Introduction: </strong>Camponotus is a diverse ant genus with over 1,500 described taxa and notable ecological and chromosomal variation. Some species display polymorphism of chromosome number, such as Camponotus rufipes which has individuals with 2n=40 and 2n=39 within the same nest. This variation is thought to result from a Robertsonian fusion between two subtelocentric chromosomes, forming a large metacentric chromosome.</p><p><strong>Methods: </strong>We performed the chromosomal mapping of the telomeric motif (TTAGG)n, highly and moderately repetitive DNA isolated from the C. rufipes genome (C0t-DNA) and the microsatellites (GA)n, and (GAG)n across both C. rufipes karyotypes (2n=40 and 2n=39). Furthermore, chromosomal measurements were obtained for both karyotypes. This analysis sought to undertand the chromosomal rearrangement that gives rise to karyotypic variation and to investigate the diversity and chromosomal organization of some repetitive sequences in this species.</p><p><strong>Results: </strong>The (TTAGG)n motif was exclusively detected at the terminal regions of the chromosomes, with no interstitial signals, consistent with the pattern typically observed in Formicidae. The C0t-DNA probe revealed signals at the centromeres of all chromosomes, including the rearranged metacentric chromosome in the 2n=39 karyotype, as well as on the short arms of subtelocentric and telocentric chromosomes, coinciding with the heterochromatin distribution previously reported for C. rufipes. Microsatellite probes exhibited a general distribution throughout the euchromatic regions, including both arms of submetacentric pairs, the rearranged metacentric chromosome, and the long arm of subtelocentric/telocentric chromosomes. Chromosomal measurements suggested the involvement of the third and either the sixth or seventh subtelocentric chromosome pairs in the rearrangement.</p><p><strong>Conclusion: </strong>We explore how the distribution of repetitive sequences suggests that the 2n=39 karyotype in C. rufipes resulted from a Robertsonian fusion. We provide the first data on the diversity and organization of some repetitive sequences in C. rufipes, as well as in Formicinae, highlighting their potential contribution to understanding chromosomal evolution in ants.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105503","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":"A Familial 22.59 Mb Deletion of the 10q11.21q21.3 Region on the Neocentromeric Chromosome 10 with Coexistence of Small Marker Chromosome (10): Case Report and Review of Literature.","authors":"Joanna Bernaciak, Marta Ewa Kędzior, Kamila Ziemkiewicz, Izabela Plaskota, Barbara Wiśniowiecka-Kowalnik, Maria Boczar, Ewa Obersztyn, Beata Anna Nowakowska","doi":"10.1159/cgr/achag008","DOIUrl":"10.1159/cgr/achag008","url":null,"abstract":"<p><strong>Introduction: </strong>We report a boy with intellectual disability and dysmorphic features carrying an interstitial 22.59 Mb deletion of the 10q11.21q21.3 region that contains 95 coding genes.</p><p><strong>Case presentation: </strong>The 8-year-old-male patient is the second child born from the third pregnancy to. non-consanguineous parents. The aberration was inherited from a 34-year-old phenotypically normal father in whom cytogenetic and molecular analyses revealed a mosaic karyotype, with 2 cell lines: - deletion of the 10q11.21q21.3 region in the neocentromeric chromosome 10 in all cells and an extra small marker chromosome (SMC) derived from chromosome 10 in 50% of analyzed cells.</p><p><strong>Conclusion: </strong>To our best knowledge, the father of our patient is the first person described with a 10q11.21q21.3 deletion and the presence of a marker chromosome derived from this region. A literature review of patients with deletion in this region and the mechanism of such a chromosomal rearrangement are discussed herein.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001454","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":"Comparative Cytogenetics of Crocidura Species: C. kegoensis, C. dracula, and C. sibirica (Soricidae, Eulipotyphla).","authors":"Larisa S Biltueva, Natalya A Lemskaya, Alexei V Abramov, Dinh The Dung, Natalia A Serdukova, Anastasia A Proskuryakova, Vladimir A Trifonov, Jorge Pereira, Svetlana A Romanenko","doi":"10.1159/cgr/achag005","DOIUrl":"10.1159/cgr/achag005","url":null,"abstract":"<p><strong>Introduction: </strong>Cytogenetic variation and chromosomal evolution in Palearctic white-toothed shrews (Crocidura) remain poorly understood, particularly within the Asian clade. Here, we provide the first cytogenetic characterization of Crocidura kegoensis and Crocidura dracula from Vietnam.</p><p><strong>Methods: </strong>To enable comparative analysis within and beyond the genus, we generated a flow-sorted library for C. sibirica and applied fluorescent in situ hybridization to C. dracula metaphase chromosomes.</p><p><strong>Results: </strong>All studied C. kegoensis individuals have stable karyotypes with 2n=40 and FNa = 52 and are distinguished by large heterochromatic blocks on sex chromosomes. Different C. dracula specimens with equal FNa = 52 have 2n=36-38 due to centromeric fusions.</p><p><strong>Conclusions: </strong>Integrating our cytogenetic data with existing genetic evidence, we confirmed the presence of two distinct groups within the Asian clade of Palearctic Crocidura - northwestern and southeastern - that differ both genetically and karyologically. Using C. dracula as a focal taxon, we highlight ongoing, rapid speciation within the southeastern group and show that the extent of chromosomal rearrangements in taxa correlates with their divergence time.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879345","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":"Comparative Analysis of the Karyotypes of <i>Equus caballus</i> and <i>Equus asinus</i> in the Context of Contemporary Genomic Data.","authors":"Wiktoria Kowal-Mierzwa, Monika Bugno-Poniewierska","doi":"10.1159/cgr/achag004","DOIUrl":"10.1159/cgr/achag004","url":null,"abstract":"<p><strong>Background: </strong>Karyotypes of species within the genus Equus display considerable variation in chromosome number and are characterised by numerous structural rearrangements that have played a pivotal role in their evolutionary divergence and speciation. Equus caballus (horse), 2n = 64 and Equus asinus (donkey), 2n = 62, constitute particularly interesting models for comparative studies due to the diversified morphology of their chromosomes, including acrocentric and submetacentric pairs, documented Robertsonian translocations, and centric fusions.</p><p><strong>Summary: </strong>In recent decades, widely applied molecular cytogenetic techniques, especially fluorescence in situ hybridisation (FISH), have enabled the identification of homologous regions, the determination of breakpoint locations, and the precise mapping of chromosomal fragments. Simultaneously, the rapid development of sequencing technologies has allowed for the generation of complete genomic assemblies and the detection of numerous rearrangements that were not identified by earlier methods. Despite these advances, comprehensive physical validation of the most variable chromosomal regions in both species is still lacking, which limits a full understanding of karyotype dynamics and its evolutionary significance.</p><p><strong>Key messages: </strong>For this reason, further studies involving systematic bacterial artificial chromosome probe mapping and the integration of FISH data with advanced genomic techniques are warranted. Such an interdisciplinary framework would facilitate the construction of a high-resolution physical map of the genomes of E. caballus and E. asinus, thereby advancing our understanding of the mechanisms underlying speciation within the genus Equus.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789465","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":"Paternal Transmission of Angelman Syndrome via a Mosaic Small Supernumerary Marker Chromosome 15: A Rare Case of Germline Epigenetic Reset Failure and Somatic Rescue.","authors":"Mohammed Alraddadi, Lama Almohlesy, Areej Ashour, Asma Alsalamah, Sahar Ramadan, Yara Alqahtani, Mohammed Alowain, Wafa Alqubbaj, Haitham Khogeer, Ines Ben Abdallah Bouhjar","doi":"10.1159/cgr/achag003","DOIUrl":"10.1159/cgr/achag003","url":null,"abstract":"<p><strong>Introduction: </strong>Angelman syndrome (AS) is an imprinting disorder that arises almost exclusively through maternal mechanisms; most commonly maternal 15q11.2-q13 deletion; less often, paternal uniparental disomy (UPD) of chromosome 15. Paternal transmission of a 15q11.2-q13 deletion typically results in Prader-Willi syndrome, making familial paternal AS transmission exceptionally rare. Herein, we report a pedigree in which a neurotypical father transmitted AS to multiple offspring via a structural mechanism distinct from UPD.</p><p><strong>Case presentation: </strong>The progenitor exhibited 47,XY,+mar[24]/46,XY [6] mosaicism by G-banding karyotype, with three distinct cell lines identified by fluorescence in situ hybridization analysis: a deleted lineage (SNRPN-; 25%), a balanced lineage (SNRPN+ on sSMC; 45%), and a dosage-rich lineage (SNRPN++ on sSMC; 30%). The sSMC is proposed to have originated through a trisomic rescue event; in which an initial trisomy 15 conceptus underwent rescue with retention of deleted region material on the marker, enabling somatic compensation in the progenitor. Notably, UPD was excluded as the pathogenic mechanism in affected offspring. Instead, the sSMC's mitotic instability likely facilitated transmission of the unbalanced deletion without the compensatory marker, whereas its structural interference with the imprinting center prevented the maternal-to-paternal epigenetic reset, resulting in an AS phenotype.</p><p><strong>Conclusion: </strong>This report highlights the role of sSMCs in masking pathogenic deletions and underscores the diagnostic importance of high-resolution genomic mapping in cases of atypical imprinting transmission.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789462","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":"Clone-Specific Cytogenetic Features Revealed by a New Repetitive Marker in Dojo Loach.","authors":"Kiko Shibata, Masamichi Kuroda, Toshiya Nishimura, Etsuro Yamaha, Katsutoshi Arai, Takafumi Fujimoto","doi":"10.1159/000552480","DOIUrl":"10.1159/000552480","url":null,"abstract":"<p><strong>Introduction: </strong>Most fish reproduce sexually, but some species reproduce asexually through gynogenesis. Gynogenetic species are thought to provide important insight into the evolution of sexual reproduction, and investigations into their origins are required. Clonal loaches exist in certain areas of Japan and may have resulted from a past hybridization event between the two genetically divergent groups (A and B). However, the intergroup hybrids between current groups A and B show patterns different from those of clonal loaches, and comparisons distinguishing the ancestral group within clonal loaches from the current group are needed.</p><p><strong>Methods: </strong>We used NGS data to search for repetitive sequences that could serve as markers to reveal genetic differences between species and populations and developed new cytogenetic marker, M407.</p><p><strong>Results: </strong>The karyotypes and 18S rDNA signals were conserved across all examined individuals. M407 signals were detected in group B and in the ancestral groups A and B of clonal loaches but not in the current group A.</p><p><strong>Conclusion: </strong>Cytogenetic results suggest that sequences associated with group B may have been introgressed or structurally incorporated into the ancestral group A genome during hybridization events, leading to the formation of clonal loaches.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711751","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":"Integrating Optical Genome Mapping into the Genetic Diagnostic Algorithm: Clinical Utility in Unresolved Autosomal Recessive Disorders from a Large Cohort.","authors":"Ozge Beyza Gundogdu Ogutlu, Hasan Huseyin Kazan, Mehmet Burak Mutlu, Mehmet Ali Ergun, Sengul Ozdek, Gulsum Kayhan","doi":"10.1159/cgr/achag002","DOIUrl":"10.1159/cgr/achag002","url":null,"abstract":"<p><strong>Introduction: </strong>The identification of precise genetic etiologies is indispensable for the clinical management of monogenic disorders. However, conventional diagnostic methods and exome sequencing (ES) frequently fail to identify complex structural variations (SVs), leaving the genetic basis unexplained in approximately 30-60% of suspected cases. Optical genome mapping (OGM) emerges as a high-resolution technology capable of detecting cryptic SVs inaccessible to standard methodologies.</p><p><strong>Methods: </strong>In this study, we evaluated the clinical utility of integrating OGM into the diagnostic algorithm for unresolved monogenic diseases. Following negative or inconclusive results from standard ES pipelines, OGM was applied to a targeted subset of patients (n = 7) selected from a comprehensive clinical cohort of 1,257 individuals with suspected genetic disorders.</p><p><strong>Results: </strong>The integration of OGM identified candidate SVs that may represent the second allelic alteration in two distinct cases; however, confirmation through parental segregation analysis remains pending. Specifically, OGM identified an intronic insertion in the TTLL5 gene and a deletion in a putative regulatory region approximately 400 kb upstream of the NMNAT1 gene, both of which were missed by prior diagnostic testing.</p><p><strong>Conclusion: </strong>Our findings suggest that OGM has potential value in investigating the missing heritability of autosomal recessive disorders. By detecting candidate SVs invisible to conventional methods, OGM may warrant consideration as a complementary diagnostic approach following inconclusive ES; however, larger cohorts and confirmatory functional studies are needed to establish its clinical utility.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":" ","pages":"1"},"PeriodicalIF":2.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648428","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}