{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:35:37Z","timestamp":1791477337301,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic>. However, in 10%\u201315% of patients with clinically confirmed TSC, no <jats:italic>TSC1<\/jats:italic>\/<jats:italic>TSC2<\/jats:italic> variants are identified by panel sequencing or multiplex ligation\u2010dependent probe amplification (MLPA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed eight fetuses with CR and their families. No <jats:italic>TSC1<\/jats:italic>\/<jats:italic>TSC2<\/jats:italic> variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next\u2010generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four fetuses carried low\u2010level mosaic variants (0.05%\u201314.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second\u2010hit variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The fetuses assessed in this study carried low<jats:bold>\u2010<\/jats:bold>level and somatic mosaic variants, and CR tissue from one fetus exhibited a second\u2010hit variant. Heterozygous gonadal variants can exist in patients with low\u2010level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1802","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T08:58:05Z","timestamp":1630745885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Detection of <i>TSC1<\/i>\/<i>TSC2<\/i> mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid\u2010capture next\u2010generation sequencing"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9152-451X","authenticated-orcid":false,"given":"Siyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Echocardiography Beijing An Zhen Hospital Capital Medical University Beijing China"},{"name":"Department of Medical Ultrasonics Beijing Chao Yang Hospital Capital Medical University Beijing 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