Detection of Clinically Relevant Monogenic Copy-Number Variants by a Comprehensive Genome-Wide Microarray with Exonic Coverage.
Background Disease-causing copy-number variants (CNVs) often encompass contiguous genes and can be detected using chromosomal microarray analysis (CMA). Conversely, CNVs affecting single disease-causing genes have historically been challenging to detect due to their small sizes. Methods A custom com...
| Publicado en: | Clinical Chemistry Vol. 71; no. 1; pp. 141 - 155 |
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| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Oxford University Press / USA
Jan2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=182092255&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 182092255 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00099147 10CS jtl: Clinical Chemistry issn: 00099147 maglogo: N pubinfo: dt: Jan2025 vid: 71 iid: 1 pid: 622 pub: Oxford University Press / USA artinfo: ui: 182092255 10.1093/clinchem/hvae188 182092255 ppf: 141 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Detection of Clinically Relevant Monogenic Copy-Number Variants by a Comprehensive Genome-Wide Microarray with Exonic Coverage. aug: au: Chau, Matthew Hoi Kin Anderson, Stephanie A Song, Rodger Cooper, Lance Ward, Patricia A Yuan, Bo Shaw, Chad Stankiewicz, Paweł Cheung, Sau Wai Vossaert, Liesbeth Wang, Yue Owen, Nichole M Smith, Janice Bacino, Carlos A Schulze, Katharina V Bi, Weimin affil: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States sug: ab: Background Disease-causing copy-number variants (CNVs) often encompass contiguous genes and can be detected using chromosomal microarray analysis (CMA). Conversely, CNVs affecting single disease-causing genes have historically been challenging to detect due to their small sizes. Methods A custom comprehensive CMA (Baylor College of Medicine - BCM v11.2) containing 400k probes and featuring exonic coverage for >4200 known or candidate disease-causing genes was utilized for the detection of CNVs at single-exon resolution. CMA results across a consecutive clinical cohort of more than 13 000 patients referred for genetic investigation at Baylor Genetics were examined. The genomic characteristics of CNVs impacting single protein-coding genes were investigated. Results Pathogenic or likely pathogenic (P/LP) CNVs (n = 190) affecting single protein-coding genes were detected in 188 patients, accounting for 9.9% (188/1894) of patients with P/LP CMA findings. The P/LP monogenic CNVs accounted for 9.2% (190/2058) of all P/LP nuclear CNVs detected by CMA. A total of 57.9% (110/190) of P/LP monogenic CNVs were smaller than 50 kb in size. Single exons were affected by 26.3% (50/190) of P/LP monogenic CNVs while 13.2% (25/190) affected 2 exons. CNVs were detected across 107 unique genes associated with predominantly autosomal dominant (AD) and X-linked (XL) conditions but also contributed to autosomal recessive (AR) conditions. Conclusions CMA with exon-targeted coverage of disease-associated genes facilitated the detection of small CNVs affecting single protein-coding genes, adding substantial clinical sensitivity to comprehensive CNV investigation. This approach resolved monogenic CNVs associated with autosomal and X-linked monogenic etiologies and yielded multiple significant findings. Monogenic CNVs represent an underrecognized subset of disease-causing alleles for Mendelian disorders. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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