{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:27Z","timestamp":1791041907030,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome is a so\u2010called \u201cRASopathy,\u201d that is characterized by short stature, distinctive facial features, congenital heart defects, and developmental delay. Of individuals with a clinical diagnosis of Noonan syndrome, 80%\u201390% have pathogenic variants in the known genes implicated in the disorder, but the molecular mechanism is unknown in the remaining cases. Heterozygous pathogenic variants of ETS2 repressor factor (<jats:italic>ERF<\/jats:italic>), which functions as a repressor in the RAS\/MAPK signaling pathway, cause syndromic craniosynostosis. Here, we report an <jats:italic>ERF<\/jats:italic> frameshift variant cosegregating with a Noonan syndrome\u2010like phenotype in a family. The proband was a 3\u2010year\u2010old female who presented with dysmorphic facial features, including proptosis, hypertelorism, slightly down slanted palpebral fissures, low\u2010set posteriorly rotated ears, depressed nasal bridge, short stature, and developmental delay. Exome sequencing of the proband identified a heterozygous <jats:italic>ERF<\/jats:italic> variant [NM_006494.4: c.185del p.(Glu62Glyfs*15)]. Her mother and sister showed a similar phenotype and had the same heterozygous <jats:italic>ERF<\/jats:italic> variant. A large proportion of the previously reported patients with syndromic craniosynostosis and pathogenic <jats:italic>ERF<\/jats:italic> variants also showed characteristic features that overlap with those of Noonan syndrome. The present finding supports an association between heterozygous <jats:italic>ERF<\/jats:italic> variants and a Noonan syndrome\u2010like phenotype.<\/jats:p>","DOI":"10.1002\/ajmg.a.63652","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T07:13:44Z","timestamp":1715670824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Noonan syndrome\u2010like phenotype associated with an <i>ERF<\/i> frameshift variant"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1789-3431","authenticated-orcid":false,"given":"Yasuhiro","family":"Hirano","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hiratsuka City Hospital  Hiratsuka Kanagawa Japan"},{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-6070","authenticated-orcid":false,"given":"Yukiko","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Clinical Research Institute Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Naruto","sequence":"additional","affiliation":[{"name":"Clinical Research Institute Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Muroya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7748","authenticated-orcid":false,"given":"Kenji","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37259"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38070"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35270"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0922"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37218"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/2333794X19846774"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61073"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-020-01015-z"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32786"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.24.3.1206-1218.2004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-008-0858-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.13329"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62900"},{"key":"e_1_2_10_15_1","first-page":"1993","volume-title":"GeneReviews at GeneTests Medical Genetics Information Resource (database online","author":"Roberts A. 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