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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP-
dc.contributor.authorKUREK, Kyle C.-
dc.contributor.authorLUKS, Valerie L.-
dc.contributor.authorAYTURK, Ugur M.-
dc.contributor.authorALOMARI, Ahmad I.-
dc.contributor.authorFISHMAN, Steven J.-
dc.contributor.authorSPENCER, Samantha A.-
dc.contributor.authorMULLIKEN, John B.-
dc.contributor.authorBOWEN, Margot E.-
dc.contributor.authorYAMAMOTO, Guilherme L.-
dc.contributor.authorKOZAKEWICH, Harry P. W.-
dc.contributor.authorWARMAN, Matthew L.-
dc.identifier.citationAMERICAN JOURNAL OF HUMAN GENETICS, v.90, n.6, p.1108-1115, 2012-
dc.description.abstractCongenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies (CLOVES) is a sporadically occurring, nonhereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. We hypothesized that CLOVES syndrome would be caused by a somatic mutation arising during early embryonic development. Therefore, we employed massively parallel sequencing to search for somatic mosaic mutations in fresh, frozen, or fixed archival tissue from six affected individuals. We identified mutations in PIK3CA in all six individuals, and mutant allele frequencies ranged from 3% to 30% in affected tissue from multiple embryonic lineages. Interestingly, these same mutations have been identified in cancer cells, in which they increase phosphoinositide-3-kinase activity. We conclude that CLOVES is caused by postzygotic activating mutations in PIK3CA. The application of similar sequencing strategies will probably identify additional genetic causes for sporadically occurring, nonheritable malformations.-
dc.description.sponsorshipManton Center for Orphan Disease Research [94824-01]-
dc.description.sponsorshipBoston Children's Hospital-
dc.description.sponsorshipNational Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS) [AR053237]-
dc.description.sponsorshipHoward Hughes Medical Institute-
dc.publisherCELL PRESS-
dc.relation.ispartofAmerican Journal of Human Genetics-
dc.subject.otherhematopoietic stem-
dc.titleSomatic Mosaic Activating Mutations in PIK3CA Cause CLOVES Syndrome-
dc.rights.holderCopyright CELL PRESS-
dc.subject.wosGenetics & Heredity-
dc.type.categoryoriginal article-
dc.type.versionpublishedVersion-, Kyle C.:Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA-, Valerie L.:Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA-, Ugur M.:Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA; Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA-, Ahmad I.:Boston Childrens Hosp, Dept Vasc & Intervent Radiol, Boston, MA 02115 USA; Boston Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02115 USA-, Steven J.:Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA; Boston Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02115 USA-, Samantha A.:Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA-, John B.:Boston Childrens Hosp, Dept Plast Surg, Boston, MA 02115 USA-, Margot E.:Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA; Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA-, Harry P. W.:Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA; Boston Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02115 USA-, Matthew L.:Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA; Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA; Boston Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02115 USA; Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA-
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