{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:12:10Z","timestamp":1791871930458,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Somatic overgrowth conditions, including Proteus syndrome, Sturge\u2013Weber syndrome, and <jats:italic>PIK3CA<\/jats:italic>\u2010related overgrowth spectrum, are caused by post\u2010zygotic pathogenic variants, result in segmental mosaicism, and give rise to neural, cutaneous and\/or lipomatous overgrowth. These variants occur in growth\u2010promoting pathways leading to cellular proliferation and expansion of tissues that arise from the affected cellular lineage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report on 80 serial patients evaluated for somatic overgrowth conditions in a diagnostic laboratory setting, including three prenatal patients. In total, 166 tissues from these 80 patients were subjected to targeted sequencing of an 8\u2010gene panel capturing 10.2\u00a0kb of sequence containing known pathogenic variants associated with somatic overgrowth conditions. Deep next\u2010generation sequencing was performed with the IonTorrent PGM platform at an average depth typically &gt;5,000\u00d7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Likely pathogenic or pathogenic variants were identified in 36 individuals and variants of unknown significance in four. The overall molecular diagnostic yield was 45% but was highly influenced by both submitted tissue type and phenotype. In the prenatal setting, two patients had pathogenic variants identified in cultured amniocytes but in a third patient, the pathogenic variant was only present in post\u2010natal tissues. Finally, expanding the test to include full gene sequencing of <jats:italic>PIK3CA<\/jats:italic> in contrast to targeted sequencing identified likely pathogenic variants in 3 of 7 patients that tested negative on the original panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Next\u2010generation sequencing has enabled sensitive detection of somatic pathogenic variants associated with overgrowth conditions. However, as the pathogenic variant allele frequency varies by tissue type within an individual, submission of affected tissue(s) greatly increases the chances of a molecular diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.536","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T05:13:44Z","timestamp":1550121224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Molecular diagnosis of somatic overgrowth conditions: A single\u2010center experience"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8573-1966","authenticated-orcid":false,"given":"Emilie","family":"Lalonde","sequence":"first","affiliation":[{"name":"Genetic Diagnostic Laboratory, Department of Genetics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Ebrahimzadeh","sequence":"additional","affiliation":[{"name":"Genetic Diagnostic Laboratory, Department of Genetics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Rafferty","sequence":"additional","affiliation":[{"name":"Genetic Diagnostic Laboratory, Department of Genetics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Richards\u2010Yutz","sequence":"additional","affiliation":[{"name":"Genetic Diagnostic Laboratory, Department of Genetics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Grant","sequence":"additional","affiliation":[{"name":"Genetic Diagnostic Laboratory, Department of Genetics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Toorens","sequence":"additional","affiliation":[{"name":"Penn Genomic Analysis Core, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Marie Rosado","sequence":"additional","affiliation":[{"name":"Penn Genomic Analysis Core, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Schindewolf","sequence":"additional","affiliation":[{"name":"Center for Fetal Diagnosis and Treatment Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapan","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Penn Genomic Analysis Core, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Kalish","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania"},{"name":"Department of Pediatrics, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Deardorff","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania"},{"name":"Department of Pediatrics, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arupa","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Genetic Diagnostic Laboratory, Department of Genetics University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2017.04.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3424"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","unstructured":"Cerami E. 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