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Trio genome sequencing (GS) identified three molecular diagnoses in this individual: compound heterozygous missense variants associated with polymerase III (Pol III)\u2013related leukodystrophy, a 4-Mb de novo copy-number loss including the <jats:italic>MYCN<\/jats:italic> gene associated with Feingold syndrome, and a mosaic single-nucleotide variant associated with <jats:italic>COL2A1<\/jats:italic>-related disorders. These variants fully account for the individual's features, but also illustrate the potential for superimposed and unclear contributions of multiple diagnoses to an individual's overall presentation. This report demonstrates the advantage of GS in detection of multiple variant types, including low-level mosaic variants, and emphasizes the need for comprehensive genetic analysis and detailed clinical phenotyping to provide individuals and their families with the maximum benefit for clinical care and genetic counseling.<\/jats:p>","DOI":"10.1101\/mcs.a006143","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T18:20:14Z","timestamp":1636050014000},"page":"a006143","source":"Crossref","is-referenced-by-count":5,"title":["Genome sequencing identifies three molecular diagnoses including a mosaic variant in the <i>COL2A1<\/i> gene in an individual with Pol III\u2013related leukodystrophy and Feingold syndrome"],"prefix":"10.1101","volume":"7","author":[{"given":"Kayla J.","family":"Muirhead","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda R.","family":"Clause","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zinayida","family":"Schlachetzki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Dubbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise L.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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