{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:32:56Z","timestamp":1794047576414,"version":"4.8.0"},"reference-count":34,"publisher":"BMJ","issue":"12","funder":[{"name":"CIFRE","award":["ANR-19-P3IA-0003"],"award-info":[{"award-number":["ANR-19-P3IA-0003"]}]},{"DOI":"10.13039\/501100003032","name":"ANRT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,8,10]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite the availability of whole exome (WES) and genome sequencing (WGS), chromosomal microarray (CMA) remains the first-line diagnostic test in most rare disorders diagnostic workup, looking for copy number variations (CNVs), with a diagnostic yield of 10%\u201320%. The question of the equivalence of CMA and WES in CNV calling is an organisational and economic question, especially when ordering a WGS after a negative CMA and\/or WES.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNVs on a retrospective cohort of 615 unrelated individuals. A prospective detection of WES-CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>On the retrospective validation cohort, every CNV detectable by the method (ie, a CNV with at least one exon not in a dark zone) was accurately called (64\/64 events). In the prospective cohort, 32 diagnoses were performed among the 2418 individuals with CNVs ranging from 704\u2009bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2022-108439","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T13:26:12Z","timestamp":1663853172000},"page":"1234-1240","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases"],"prefix":"10.1136","volume":"59","author":[{"given":"Quentin","family":"Testard","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Eurofins Biomnis, Lyon, France"},{"name":"Service de G\u00e9n\u00e9tique et Procr\u00e9ation, CHU Grenoble Alpes, Grenoble, France"},{"name":"CNRS UMR 5309, INSERM, U1209, Universit\u00e9 Grenoble Alpes, 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