{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:41:14Z","timestamp":1790109674272,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T00:00:00Z","timestamp":1730592000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Key Clinical Message<\/jats:title>\n                    <jats:p>\n                      Not only germline but also postzygotic mutations in the\n                      <jats:italic>RASA1<\/jats:italic>\n                      or\n                      <jats:italic>EPHB4<\/jats:italic>\n                      genes can lead to capillary malformation\u2010arteriovenous malformation (CM\u2010AVM) syndrome. As it is not always possible to clinically distinguish between constitutional variants and postzygotic mosaicism, a sufficiently high sequencing depth must be used in genetic diagnostics to detect both.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Capillary malformation\u2010arteriovenous malformation (CM\u2010AVM) syndrome, with or without Parkes Weber syndrome, is a rare autosomal dominant disease caused by pathogenic\n                      <jats:italic>RASA1<\/jats:italic>\n                      or\n                      <jats:italic>EPHB4<\/jats:italic>\n                      variants. Up to 80% of CM\u2010AVM cases have an affected parent. Gene panel sequencing was performed for a 4\u2010year\u2010old girl with multiple CMs, two capillary stains on the left leg, and associated overgrowth of the second toe. We also reviewed published cases with mosaic\n                      <jats:italic>RASA1<\/jats:italic>\n                      and\n                      <jats:italic>EPHB4<\/jats:italic>\n                      mutations. A mosaic\n                      <jats:italic>RASA1<\/jats:italic>\n                      loss\u2010of\u2010function mutation was detected with a variant allele frequency (VAF) of 20% in the blood and oral epithelial cells of the index patient. The literature review illustrates that the severity of the clinical phenotype does not correlate with the VAF. We also identified a germline nonsense variant in the patient's\n                      <jats:italic>TEK<\/jats:italic>\n                      gene. However, inactivating\n                      <jats:italic>TEK<\/jats:italic>\n                      variants do not cause a vascular phenotype but can confer an increased risk for primary congenital glaucoma with variable expressivity. The case presented here illustrates that the choice of the sequencing depth of a diagnostic next\u2010generation sequencing test for CM\u2010AVM patients should always take mosaicism into account and that a good knowledge of the sequenced genes and associated disease mechanisms is necessary for adequate genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ccr3.9543","type":"journal-article","created":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T23:39:32Z","timestamp":1730677172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel postzygotic\n                    <i>RASA1<\/i>\n                    mutation in a patient with Parkes Weber syndrome: A case report and literature review"],"prefix":"10.1002","volume":"12","author":[{"given":"Robin A.","family":"Pilz","sequence":"first","affiliation":[{"name":"Department of Human Genetics University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariush","family":"Skowronek","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Ehresmann","sequence":"additional","affiliation":[{"name":"Limbach Genetics GmbH MVZ Humangenetik  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Felbor","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-4650","authenticated-orcid":false,"given":"Matthias","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald  Greifswald Germany"},{"name":"Institute for Molecular Medicine, MSH Medical School Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.026886"},{"key":"e_1_2_13_4_1","volume-title":"GeneReviews\u00ae","author":"Bayrak\u2010Toydemir 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