{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:26:20Z","timestamp":1787214380544,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDDs) are characterized by a complex genetic architecture involving both rare high-impact variants and cumulative low-effect alterations. The contribution of borderline copy number variants (CNVs) to disease susceptibility and phenotypic variability remains incompletely understood. Reflecting a real-world clinical setting rather than a prospectively recruited research cohort, we performed a retrospective analysis of a tertiary care registry comprising 328 individuals referred for suspected ASD or NDDs who underwent array comparative genomic hybridization (a-CGH), identifying 612 CNVs classified according to ACMG\/ClinGen guidelines. CNVs were evaluated by type, size, genomic distribution, and clinical correlation, and patients were stratified based on CNV burden and the presence of borderline variants. Duplications were more frequent than deletions, and medium-sized CNVs (100\u2013500 kb) were the most common. Borderline CNVs represented the largest category. Within this descriptive cohort, increased CNV burden, in both number and cumulative genomic size, co-occurred more frequently in individuals with severe phenotypes, including ASD with intellectual disability, epilepsy, and broader NDDs. Individuals with isolated ASD showed a lower burden and enrichment of small borderline variants, which often co-occurred alongside CNVs. In contrast, severe phenotypes were frequently associated with single large pathogenic variants. Recurrent loci included 15q11.2\u2013q13, 16p11.2, and 22q11.21. Overall, these exploratory observations from a real-world clinical registry illustrate how cumulative genomic burden and borderline CNVs co-occur across different neurodevelopmental presentations, providing descriptive context for future mechanistic studies.<\/jats:p>","DOI":"10.3390\/ijms27167434","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:10:20Z","timestamp":1787213420000},"page":"7434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contribution of Copy Number Variants and Cumulative Genetic Load to Autism Spectrum Disorders: Integrative Insights from Chromosomal Microarray Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7321-9799","authenticated-orcid":false,"given":"Maria Rosaria","family":"Di Iorio","sequence":"first","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1072-3763","authenticated-orcid":false,"given":"Ilaria","family":"La Monica","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9010-5282","authenticated-orcid":false,"given":"Antonio","family":"Imperatore","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3486-3805","authenticated-orcid":false,"given":"Antonia","family":"Sica","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7541-1662","authenticated-orcid":false,"given":"Valerio","family":"Iorio","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6894-9317","authenticated-orcid":false,"given":"Lucio","family":"Pastore","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-1043","authenticated-orcid":false,"given":"Barbara","family":"Lombardo","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mullin, A.P., Gokhale, A., Moreno-De-Luca, A., Sanyal, S., Waddington, J.L., and Faundez, V. (2013). Neurodevelopmental disorders: Mechanisms and boundary definitions from genomes, interactomes and proteomes. Transl. Psychiatry, 3.","DOI":"10.1038\/tp.2013.108"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.1093\/hmg\/ddr243","article-title":"Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders","volume":"20","author":"Schaaf","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","first-page":"100919","article-title":"Contemplating syndromic autism","volume":"25","author":"Vorstman","year":"2023","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/mp.2014.141","article-title":"Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons","volume":"20","author":"Acab","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1101\/gr.3677206","article-title":"Copy number variation: New insights in genome diversity","volume":"16","author":"Freeman","year":"2006","journal-title":"Genome Res."},{"key":"ref_6","first-page":"777","article-title":"An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities","volume":"13","author":"Kaminsky","year":"2011","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R57","DOI":"10.1093\/hmg\/ddl057","article-title":"Structural variants: Changing the landscape of chromosomes and design of disease studies","volume":"15","author":"Feuk","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","first-page":"245","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Servetti, M., Pisciotta, L., Tassano, E., Cerminara, M., Nobili, L., Boeri, S., Rosti, G., Lerone, M., Divizia, M.T., and Ronchetto, P. (2021). Neurodevelopmental Disorders in Patients with Complex Phenotypes and Potential Complex Genetic Basis Involving Non-Coding Genes, and Double CNVs. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.732002"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.jmoldx.2022.06.005","article-title":"Utility and Outcomes of the 2019 American College of Medical Genetics and Genomics-Clinical Genome Resource Guidelines for Interpretation of Copy Number Variants with Borderline Classifications at an Academic Clinical Diagnostic Laboratory","volume":"24","author":"Drackley","year":"2022","journal-title":"J. Mol. Diagn."},{"key":"ref_11","first-page":"399","article-title":"Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions","volume":"15","author":"Schaefer","year":"2013","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ranieri, A., La Monica, I., Di Iorio, M.R., Lombardo, B., and Pastore, L. (2024). Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders. Genes, 15.","DOI":"10.3390\/genes15040427"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ranieri, A., Veneruso, I., La Monica, I., Pascale, M.G., Pastore, L., D\u2019Argenio, V., and Lombardo, B. (2022). Combined aCGH and Exome Sequencing Analysis Improves Autism Spectrum Disorders Diagnosis: A Case Report. Medicina, 58.","DOI":"10.3390\/medicina58040522"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Girirajan, S., Brkanac, Z., Coe, B.P., Baker, C., Vives, L., Vu, T.H., Shafer, N., Bernier, R., Ferrero, G.B., and Silengo, M. (2011). Relative burden of large CNVs on a range of neurodevelopmental phenotypes. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002334"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1001\/jamapsychiatry.2022.1017","article-title":"Copy Number Variant Risk Scores Associated with Cognition, Psychopathology, and Brain Structure in Youths in the Philadelphia Neurodevelopmental Cohort","volume":"79","author":"Huguet","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s13353-011-0063-z","article-title":"Mental retardation and autism associated with recurrent 16p11.2 microdeletion: Incomplete penetrance and variable expressivity","volume":"52","author":"Patsalis","year":"2011","journal-title":"J. Appl. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ajmg.b.32441","article-title":"Explaining the variable penetrance of CNVs: Parental intelligence modulates expression of intellectual impairment caused by the 22q11.2 deletion","volume":"171","author":"Klaassen","year":"2016","journal-title":"Am. J. Med. Genetics. Part B Neuropsychiatr. Genet. Off. Publ. Int. Soc. Psychiatr. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"La Monica, I., Di Iorio, M.R., Sica, A., Rufino, F., Sotira, C., Pastore, L., and Lombardo, B. (2025). Autism Spectrum Disorder: Genetic Mechanisms and Inheritance Patterns. Genes, 16.","DOI":"10.3390\/genes16050478"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1007\/s10803-018-3552-7","article-title":"Additive Effect of Variably Penetrant 22q11.2 Duplication and Pathogenic Mutations in Autism Spectrum Disorder: To Which Extent Does the Tree Hide the Forest?","volume":"48","author":"Demily","year":"2018","journal-title":"J. Autism Dev. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rylaarsdam, L., and Guemez-Gamboa, A. (2019). Genetic Causes and Modifiers of Autism Spectrum Disorder. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00385"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ajhg.2015.11.017","article-title":"Maternal Modifiers and Parent-of-Origin Bias of the Autism-Associated 16p11.2 CNV","volume":"98","author":"Duyzend","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1515\/cclm-2017-1106","article-title":"CGH array for the identification of a compound heterozygous mutation in the CYP1B1 gene in a patient with bilateral anterior segment dysgenesis","volume":"57","author":"Lombardo","year":"2019","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41398-020-00866-7","article-title":"The role of rare compound heterozygous events in autism spectrum disorder","volume":"10","author":"Lin","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1866-1955-6-17","article-title":"A CTNNA3 compound heterozygous deletion implicates a role for \u03b1T-catenin in susceptibility to autism spectrum disorder","volume":"6","author":"Bacchelli","year":"2014","journal-title":"J. Neurodev. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Malerba, N., Towner, S., Keating, K., Squeo, G.M., Wilson, W., and Merla, G. (2018). A NGS-Targeted Autism\/ID Panel Reveals Compound Heterozygous GNB5 Variants in a Novel Patient. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00626"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0140-6736(18)31129-2","article-title":"Autism spectrum disorder","volume":"392","author":"Lord","year":"2018","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S1474-4422(15)00044-7","article-title":"Gene hunting in autism spectrum disorder: On the path to precision medicine","volume":"14","author":"Geschwind","year":"2015","journal-title":"Lancet. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14366","DOI":"10.1038\/ncomms14366","article-title":"Dosage sensitivity is a major determinant of human copy number variant pathogenicity","volume":"8","author":"Rice","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13059-017-1158-6","article-title":"Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome","volume":"18","author":"Collins","year":"2017","journal-title":"Genome Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/ng.3092","article-title":"Refining analyses of copy number variation identifies specific genes associated with developmental delay","volume":"46","author":"Coe","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrg3871","article-title":"A copy number variation map of the human genome","volume":"16","author":"Zarrei","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature09146","article-title":"Functional impact of global rare copy number variation in autism spectrum disorders","volume":"466","author":"Pinto","year":"2010","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/ng.534","article-title":"A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay","volume":"42","author":"Girirajan","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.neuron.2011.05.015","article-title":"Rare de novo and transmitted copy-number variation in autistic spectrum disorders","volume":"70","author":"Levy","year":"2011","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/ng.3039","article-title":"Most genetic risk for autism resides with common variation","volume":"46","author":"Gaugler","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41588-019-0344-8","article-title":"Identification of common genetic risk variants for autism spectrum disorder","volume":"51","author":"Grove","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.conb.2012.04.007","article-title":"A genetic model for neurodevelopmental disease","volume":"22","author":"Coe","year":"2012","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R176","DOI":"10.1093\/hmg\/ddq366","article-title":"Phenotypic variability and genetic susceptibility to genomic disorders","volume":"19","author":"Girirajan","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1038\/s41467-019-12869-0","article-title":"Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders","volume":"10","author":"Oetjens","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.neuron.2011.05.002","article-title":"Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism","volume":"70","author":"Sanders","year":"2011","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1056\/NEJMoa075974","article-title":"Autism Consortium. Association between microdeletion and microduplication at 16p11.2 and autism","volume":"358","author":"Weiss","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/mp.2012.138","article-title":"Using large clinical data sets to infer pathogenicity for rare copy number variants in autism cohorts","volume":"18","author":"Sanders","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.ajhg.2007.12.009","article-title":"Structural variation of chromosomes in autism spectrum disorder","volume":"82","author":"Marshall","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"La Monica, I., Di Iorio, M.R., Sica, A., Pastore, L., and Lombardo, B. (2026). Clinical Insights into the Neurodevelopmental Impact of 16p CNVs in an Italian Clinical Cohort. Genes, 17.","DOI":"10.3390\/genes17020247"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Iannotta, F., La Monica, I., Di Iorio, M.R., Freda, V., Sica, A., de Bartolomeis, A., Pastore, L., Iasevoli, F., and Lombardo, B. (2025). A Paradigmatic Case of Genetic Overlap Between Neurodevelopment Disorders and Schizophrenia Aligning with the Neurodevelopmental Continuum Hypothesis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26093970"},{"key":"ref_46","first-page":"209","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"5157526","author":"He","year":"2014","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/pcn.70009","article-title":"How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle","volume":"80","author":"Wang","year":"2026","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/j.1399-0004.2011.01818.x","article-title":"Towards an evidence-based process for the clinical interpretation of copy number variation","volume":"81","author":"Riggs","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ranieri, A., Mennitti, C., Falcone, N., La Monica, I., Di Iorio, M.R., Tripodi, L., Gentile, A., Vitale, M., Pero, R., and Pastore, L. (2023). Positive effects of physical activity in autism spectrum disorder: How influences behavior, metabolic disorder and gut microbiota. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1238797"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nature22047","article-title":"Cell diversity and network dynamics in photosensitive human brain organoids","volume":"5457652","author":"Quadrato","year":"2017","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2015.06.034","article-title":"FOXG1-Dependent Dysregulation of GABA\/Glutamate Neuron Differentiation in Autism Spectrum Disorders","volume":"162","author":"Mariani","year":"2015","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/ng.3863","article-title":"Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders","volume":"49","author":"Weiner","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D1331","DOI":"10.1093\/nar\/gkaf1250","article-title":"The UCSC Genome Browser database: 2026 update","volume":"54","author":"Casper","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"McGowan-Jordan, J., Simons, A., and Schmid, M. (2016). ISCN 2016: An International System for Human Cytogenomic Nomenclature 2016, Karger.","DOI":"10.1159\/isbn.978-3-318-06861-0"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"D986","DOI":"10.1093\/nar\/gkt958","article-title":"The Database of Genomic Variants: A curated collection of structural variation in the human genome","volume":"42","author":"MacDonald","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev-genom-102822-100509","article-title":"DECIPHER: Improving Genetic Diagnosis Through Dynamic Integration of Genomic and Clinical Data","volume":"24","author":"Foreman","year":"2023","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMsr1406261","article-title":"ClinGen--the Clinical Genome Resource","volume":"372","author":"Rehm","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: Public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<57::AID-HUMU12>3.0.CO;2-G","article-title":"Online Mendelian Inheritance in Man (OMIM)","volume":"15","author":"Hamosh","year":"2000","journal-title":"Hum. Mutat."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:17:23Z","timestamp":1787213843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":61,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167434"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167434","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}