{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:28:39Z","timestamp":1793802519748,"version":"4.6.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural and Science Foundation of China","award":["32270678"],"award-info":[{"award-number":["32270678"]}]},{"name":"General Research Fund","award":["14117524"],"award-info":[{"award-number":["14117524"]}]},{"name":"General Research Fund","award":["14115322"],"award-info":[{"award-number":["14115322"]}]},{"name":"Innovative and Technology Fund","award":["MHX\/003\/19"],"award-info":[{"award-number":["MHX\/003\/19"]}]},{"name":"Innovative and Technology Fund","award":["PRP\/042\/22FX"],"award-info":[{"award-number":["PRP\/042\/22FX"]}]},{"name":"Collaborative Research Fund","award":["C4062-21GF"],"award-info":[{"award-number":["C4062-21GF"]}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["SL2024A03J01550"],"award-info":[{"award-number":["SL2024A03J01550"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Medical University Clinical Research","award":["GMUCR2025-02020"],"award-info":[{"award-number":["GMUCR2025-02020"]}],"id":[{"id":"https:\/\/ror.org\/00zat6v61","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>X-linked genetic diseases affect males and females through different inheritance patterns influenced by sex, where differential methylation caused by X-chromosome inactivation can present with a range of asymptomatic, mild, and severe symptoms in females. Targeted long-read sequencing (LRS) through adaptive sampling (AS) shows robust performance in characterizing genomic composition and methylation status within the X chromosome, but it is not optimal for nonhigh-molecular-weight (non-HMW) DNA. Herein, we optimized a targeted LRS for non-HMW DNA and validated its diagnostic utility in families with X-linked genomic variants reported by routine methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty families with X-linked genetic defects reported by previous chromosomal microarray analysis and\/or low-pass genome sequencing were recruited and underwent optimized targeted LRS. Genomic variants were detected and classified along with haplotype analysis for assessing allele-specific methylation changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The AS-based protocol was optimized for DNA fragmentation with size selection, library construction, and sequencing, and demonstrated a minimum 15-fold enrichment of targets against nontargets compared with the standard AS-based protocol showing 8.1-fold enrichment. In addition, our optimized LRS detected all of the X-linked variants reported previously and revealed additional findings in 7\/20 families (35%). This led to variant reclassification in 3\/20 cases (15%) achieved through breakpoint resolution for structural variants and determination of gene methylation status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrated an AS-based protocol optimized for non-HMW DNAs that enabled the comprehensive characterization of genomic and methylation changes, highlighting its robust performance in the genomic evaluation of X-linked genetic defects with promising broader application to other disease states.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvag088","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:53:00Z","timestamp":1782863580000},"page":"1145-1160","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Investigation of X-Linked Defects with Optimized Targeted Long-Read Sequencing"],"prefix":"10.1093","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8483-8799","authenticated-orcid":false,"given":"Jia","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Chun","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Research, Birth Defects Prevention Research and Transformation Team, Maternal-Fetal Medicine Institute, Bao\u2019an Maternity and Child Health Hospital Affiliated with Jinan University School of Medicine , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine Yan Tung","family":"Law","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Research, Birth Defects Prevention Research and Transformation Team, Maternal-Fetal Medicine Institute, Bao\u2019an Maternity and Child Health Hospital Affiliated with Jinan University School of Medicine , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailei","family":"Liang","sequence":"additional","affiliation":[{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-1938","authenticated-orcid":false,"given":"Matthew Hoi Kin","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Fertility Preservation Research Center, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Fertility Preservation Research Center, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne K","family":"Kwok","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9496-2256","authenticated-orcid":false,"given":"Yuanfang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects Research, Birth Defects Prevention Research and Transformation Team, Maternal-Fetal Medicine Institute, Bao\u2019an Maternity and Child Health Hospital Affiliated with Jinan University School of Medicine , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak Yeung","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Fertility Preservation Research Center, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwong Wai","family":"Choy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Fertility Preservation Research Center, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3626-6500","authenticated-orcid":false,"given":"Zirui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , Shenzhen ,","place":["China"]},{"name":"Hong Kong Hub of Obstetric and Paediatric Excellence, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]},{"name":"Fertility Preservation Research Center, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong , Hong Kong SAR ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026110408522291700_hvag088-B1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature03440","article-title":"The DNA sequence of the human X chromosome","volume":"434","author":"Ross","year":"2005","journal-title":"Nature"},{"key":"2026110408522291700_hvag088-B2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00439-011-1011-z","article-title":"Genes that escape from X inactivation","volume":"130","author":"Berletch","year":"2011","journal-title":"Hum Genet"},{"key":"2026110408522291700_hvag088-B3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1146\/annurev-cellbio-101512-122415","article-title":"Noncoding RNAs and epigenetic mechanisms during X-chromosome inactivation","volume":"30","author":"Gendrel","year":"2014","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2026110408522291700_hvag088-B4","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s12041-015-0574-1","article-title":"X-chromosome inactivation and escape","volume":"94","author":"Disteche","year":"2015","journal-title":"J Genet"},{"key":"2026110408522291700_hvag088-B5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.gde.2015.04.002","article-title":"X-chromosome inactivation: new insights into cis and trans regulation","volume":"31","author":"Galupa","year":"2015","journal-title":"Curr Opin Genet Dev"},{"key":"2026110408522291700_hvag088-B6","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/1391807","article-title":"X-chromosome inactivation and related diseases","volume":"2022","author":"Sun","year":"2022","journal-title":"Genet Res (Camb)"},{"key":"2026110408522291700_hvag088-B7","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1212\/NXG.0000000000000045","article-title":"X-inactivation in the clinical phenotype of fragile X premutation carrier sisters","volume":"2","author":"Hall","year":"2016","journal-title":"Neurol Genet"},{"key":"2026110408522291700_hvag088-B8","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1002\/ajmg.a.36511","article-title":"Epidemiology of fragile X syndrome: a systematic review and meta-analysis","volume":"164A","author":"Hunter","year":"2014","journal-title":"Am J Med Genet A"},{"key":"2026110408522291700_hvag088-B9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13023-020-01430-8","article-title":"Global epidemiology of duchenne muscular dystrophy: an updated systematic review and meta-analysis","volume":"15","author":"Crisafulli","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"2026110408522291700_hvag088-B10","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1056\/NEJMoa1203382","article-title":"Chromosomal microarray versus karyotyping for prenatal diagnosis","volume":"367","author":"Wapner","year":"2012","journal-title":"N Engl J Med"},{"key":"2026110408522291700_hvag088-B11","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/pd.6151","article-title":"Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects","volume":"42","author":"Cao","year":"2022","journal-title":"Prenat Diagn"},{"key":"2026110408522291700_hvag088-B12","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1007\/s11427-023-2564-8","article-title":"Whole-genome sequencing identifies novel genes for autism in Chinese trios","volume":"67","author":"Chang","year":"2024","journal-title":"Sci China Life Sci"},{"key":"2026110408522291700_hvag088-B13","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1007\/s11427-026-3265-5","article-title":"Characterization of rare genomic structural variants across 2,981 genomes reveals significant involvements in recessive conditions","volume":"69","author":"Dong","year":"2026","journal-title":"Sci China Life Sci"},{"key":"2026110408522291700_hvag088-B14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1399-0004.2011.01723.x","article-title":"CGG repeat in the FMR1 gene: size matters","volume":"80","author":"Willemsen","year":"2011","journal-title":"Clin Genet"},{"key":"2026110408522291700_hvag088-B15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/cam4.22","article-title":"Strategies for discovery and validation of methylated and hydroxymethylated DNA biomarkers","volume":"1","author":"Olkhov-Mitsel","year":"2012","journal-title":"Cancer Med"},{"key":"2026110408522291700_hvag088-B16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13072-024-00558-2","article-title":"Shedding light on DNA methylation and its clinical implications: the impact of long-read-based nanopore technology","volume":"17","author":"Chera","year":"2024","journal-title":"Epigenetics Chromatin"},{"key":"2026110408522291700_hvag088-B17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41525-024-00394-z","article-title":"Assessing the efficacy of target adaptive sampling long-read sequencing through hereditary cancer patient genomes","volume":"9","author":"Nakamura","year":"2024","journal-title":"NPJ Genom Med"},{"key":"2026110408522291700_hvag088-B18","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1101\/gr.279396.124","article-title":"Measuring X-chromosome inactivation skew for X-linked diseases with adaptive nanopore sequencing","volume":"34","author":"Gocuk","year":"2024","journal-title":"Genome Res"},{"key":"2026110408522291700_hvag088-B19","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00439-020-02185-9","article-title":"Low-pass genome sequencing: a validated method in clinical cytogenetics","volume":"139","author":"Chau","year":"2020","journal-title":"Hum Genet"},{"key":"2026110408522291700_hvag088-B20","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00439-020-02210-x","article-title":"Deciphering the complexity of simple chromosomal insertions by genome sequencing","volume":"140","author":"Dong","year":"2021","journal-title":"Hum Genet"},{"key":"2026110408522291700_hvag088-B21","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41436-019-0634-7","article-title":"Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis","volume":"22","author":"Wang","year":"2020","journal-title":"Genet Med"},{"key":"2026110408522291700_hvag088-B22","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3390\/genes12040478","article-title":"Performance of cell-free DNA screening for fetal common aneuploidies and sex chromosomal abnormalities: a prospective study from a less developed autonomous region in mainland China","volume":"12","author":"Lai","year":"2021","journal-title":"Genes (Basel)"},{"key":"2026110408522291700_hvag088-B23","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/pd.6520","article-title":"Unbalanced X;Y translocations carrying SRY in prenatal settings: clinical, molecular, and cytogenetic analysis of three cases","volume":"44","author":"Liu","year":"2024","journal-title":"Prenat Diagn"},{"key":"2026110408522291700_hvag088-B24","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s10875-025-01866-2","article-title":"X-linked deficiency in ELF4 in females with skewed X chromosome inactivation","volume":"45","author":"Zhao","year":"2025","journal-title":"J Clin Immunol"},{"key":"2026110408522291700_hvag088-B25","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"2026110408522291700_hvag088-B26","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2026110408522291700_hvag088-B27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13059-020-02107-y","article-title":"Long-read-based human genomic structural variation detection with cuteSV","volume":"21","author":"Jiang","year":"2020","journal-title":"Genome Biol"},{"key":"2026110408522291700_hvag088-B28","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/s41587-023-02024-y","article-title":"Detection of mosaic and population-level structural variants with Sniffles2","volume":"42","author":"Smolka","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026110408522291700_hvag088-B29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13059-020-01968-7","article-title":"NanoVar: accurate characterization of patients\u2019 genomic structural variants using low-depth nanopore sequencing","volume":"21","author":"Tham","year":"2020","journal-title":"Genome Biol"},{"key":"2026110408522291700_hvag088-B30","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12859-023-05434-6","article-title":"Boosting variant-calling performance with multi-platform sequencing data using Clair3-MP","volume":"24","author":"Yu","year":"2023","journal-title":"BMC Bioinformatics"},{"key":"2026110408522291700_hvag088-B31","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s13059-021-02447-3","article-title":"Straglr: discovering and genotyping tandem repeat expansions using whole genome long-read sequences","volume":"22","author":"Chiu","year":"2021","journal-title":"Genome Biol"},{"key":"2026110408522291700_hvag088-B32","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nbt.4235","article-title":"A universal snp and small-indel variant caller using deep neural networks","volume":"36","author":"Poplin","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2026110408522291700_hvag088-B33","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-1-0716-2819-5_8","article-title":"Read-based phasing and analysis of phased variants with whatshap","volume":"2590","author":"Martin","year":"2023","journal-title":"Methods Mol Biol"},{"key":"2026110408522291700_hvag088-B34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1009524","article-title":"NanoMethViz: an R\/Bioconductor package for visualizing long-read methylation data","volume":"17","author":"Su","year":"2021","journal-title":"PLoS Comput Biol"},{"key":"2026110408522291700_hvag088-B35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/clinchem\/hvae146","article-title":"Mate-pair sequencing enables identification and delineation of balanced and unbalanced structural variants in prenatal cytogenomic diagnostics","volume":"71","author":"Qian","year":"2025","journal-title":"Clin Chem"},{"key":"2026110408522291700_hvag088-B36","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion","volume":"39","author":"Abou Tayoun","year":"2018","journal-title":"Hum Mutat"},{"key":"2026110408522291700_hvag088-B37","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1002\/humu.24088","article-title":"Fitting a naturally scaled point system to the ACMG\/AMP variant classification guidelines","volume":"41","author":"Tavtigian","year":"2020","journal-title":"Hum Mutat"},{"key":"2026110408522291700_hvag088-B38","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","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"},{"key":"2026110408522291700_hvag088-B39","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/humu.24009","article-title":"Int22h1\/Int22h2-mediated Xq28 duplication syndrome: de novo duplications, prenatal diagnoses, and additional phenotypic features","volume":"41","author":"Ballout","year":"2020","journal-title":"Hum Mutat"},{"key":"2026110408522291700_hvag088-B40","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/clinchem\/hvaf136","article-title":"Integrated genotyping strategies for uncovering detailed haplotype structures and characterization of DMD duplications","volume":"72","author":"Sun","year":"2026","journal-title":"Clin Chem"},{"key":"2026110408522291700_hvag088-B41","article-title":"Clinical relevance of loss-of-function mutations of NEMO\/IKBKG","volume":"12","author":"Wang","year":"2025","journal-title":"Genes Dis"},{"key":"2026110408522291700_hvag088-B42","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/35013114","article-title":"Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium","volume":"405","author":"Smahi","year":"2000","journal-title":"Nature"},{"key":"2026110408522291700_hvag088-B43","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/ajh.24545","article-title":"Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations","volume":"91","author":"Xu","year":"2016","journal-title":"Am J Hematol"},{"key":"2026110408522291700_hvag088-B44","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1002\/humu.22446","article-title":"De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy","volume":"34","author":"Kodera","year":"2013","journal-title":"Hum Mutat"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/72\/11\/1145\/70766897\/hvag088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/72\/11\/1145\/70766897\/hvag088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:52:35Z","timestamp":1793800355000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/72\/11\/1145\/8769012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":44,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,8,24]]},"published-print":{"date-parts":[[2026,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvag088","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,11]]},"published":{"date-parts":[[2026,8,24]]}}}