{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:11:22Z","timestamp":1790878282759,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T00:00:00Z","timestamp":1457654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Germline mutations in\n                      <jats:italic>RASA1<\/jats:italic>\n                      are associated with capillary malformation\u2010arteriovenous malformation (CM\u2010AVM) syndrome. CM\u2010AVM syndrome is characterized by multi\u2010focal capillary malformations and arteriovenous malformations. Lymphatic anomalies have been proposed as part of the phenotype. Intrafamilial variability has been reported, suggesting modifiers and somatic events. The objective of the study was to identify somatic\n                      <jats:italic>RASA1<\/jats:italic>\n                      \u201csecond hits\u201d from vascular malformations associated with CM\u2010AVM syndrome, and describe phenotypic variability. Participants were examined and phenotyped. Genomic DNA was extracted from peripheral blood on all participants. Whole\u2010exome sequencing was performed on the proband. Using Sanger sequencing,\n                      <jats:italic>RASA1<\/jats:italic>\n                      exon 8 was PCR\u2010amplified to track the c.1248T&gt;G, p.Tyr416X germline variant through the family. A skin biopsy of a capillary malformation from the proband's mother was also obtained, and next\u2010generation sequencing was performed on DNA from the affected tissue. A familial germline heterozygous novel pathogenic\n                      <jats:italic>RASA1<\/jats:italic>\n                      variant, c.1248T&gt;G (p.Tyr416X), was identified in the proband and her mother. The proband had capillary malformations, chylothorax, lymphedema, and overgrowth, while her affected mother had only isolated capillary malformations. Sequence analysis of DNA extracted from a skin biopsy of a capillary malformation of the affected mother showed a second\n                      <jats:italic>RASA1<\/jats:italic>\n                      somatic mutation (c.2245C&gt;T, p.Arg749X). These results and the extreme variable expressivity support the hypothesis that somatic \u201csecond hits\u201d are required for the development of vascular anomalies associated with CM\u2010AVM syndrome. In addition, the phenotypes of the affected individuals further clarify that lymphatic manifestations are also part of the phenotypic spectrum of\n                      <jats:italic>RASA1<\/jats:italic>\n                      \u2010related disorders. \u00a9 2016 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.37613","type":"journal-article","created":{"date-parts":[[2016,3,12]],"date-time":"2016-03-12T14:29:41Z","timestamp":1457792981000},"page":"1450-1454","source":"Crossref","is-referenced-by-count":106,"title":["<i>RASA1<\/i>\n                    somatic mutation and variable expressivity in capillary malformation\/arteriovenous malformation (CM\/AVM) syndrome"],"prefix":"10.1002","volume":"170","author":[{"given":"Colleen F.","family":"Macmurdo","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Wooderchak\u2010Donahue","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"},{"name":"Department of Pathology University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Bayrak\u2010Toydemir","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"},{"name":"Department of Pathology University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Le","sequence":"additional","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Wallenstein","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Milla","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce M. C.","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Dermatology Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222722110"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.01.009"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/377695a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08493.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-008-0842-5"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46116"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90976-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.12112"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37203"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20746"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22431"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000349919"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1907"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37613","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37613","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T05:49:34Z","timestamp":1696571374000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,11]]},"references-count":14,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1002\/ajmg.a.37613"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37613","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,11]]}}}