{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:48:36Z","timestamp":1770360516962,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Craniosynostosis (CS) is the premature fusion of the cranial sutures, occurring either in isolated or syndromic form. Syndromic CS, which was described in over 180 genetic syndromes, accounts for 15\u201330% of all CS cases and usually originates from mutations within the <jats:italic>FGFR1<\/jats:italic>, <jats:italic>FGFR2<\/jats:italic>, <jats:italic>FGFR3<\/jats:italic>, and <jats:italic>TWIST1<\/jats:italic> genes. However, causative alterations in other genes, or rarely copy number variations (CNVs) were also reported. In this article, we describe a patient with Noonan\u2010like facial dysmorphism accompanied by intellectual disability and compound CS, involving coronal, sagittal, and squamous sutures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied karyotyping, copy number variations analysis using array comparative genomic hybridization, and microarray\u2010based genes expresion analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have shown that the index carried a large and rare heterozygous deletion, which encompassed 12.782\u2009Mb and mapped to a chromosomal region of 7q32.3\u2010q35 (HG38 \u2013 chr7:131837067\u2010144607071). The aberration comprised 109 protein\u2010coding genes, including <jats:italic>BRAF<\/jats:italic>, that encodes serine\/threonine\u2010protein kinase B\u2010Raf, being a part of the RAS\/MAPK signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The RAS\/MAPK pathway plays an essential role in human development; hence, its dysregulation not surprisingly results in severe congenital anomalies, such as phenotypically overlapping syndromes termed RASopathies. To our best knowledge, we report here the first CNV causing haploinsufficiency of <jats:italic>BRAF<\/jats:italic>, resulting in dysregulation of the RAS\/MAPK cascade, and consequently, in the phenotype observed in our patient. To conclude, with this report, we have pointed to the involvement of the RAS\/MAPK signaling pathway in CS development. Moreover, we have shown that the molecular analysis based on both DNA and RNA profiling, undoubtedly constitutes a comprehensive diagnostic and research strategy for elucidating a cause of genetic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1744","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T12:28:55Z","timestamp":1591964935000},"page":"740-748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Compound craniosynostosis, intellectual disability, and Noonan\u2010like facial dysmorphism associated with 7q32.3\u2010q35 deletion"],"prefix":"10.1002","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-1696","authenticated-orcid":false,"given":"Ewelina","family":"Bukowska\u2010Olech","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Poznan Poland"},{"name":"Postgraduate School of Molecular Medicine Medical University of Warsaw  Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0493-8325","authenticated-orcid":false,"given":"Monika","family":"Dmitrzak\u2010W\u0119glarz","sequence":"additional","affiliation":[{"name":"Department of Genetics in Psychiatry Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-9106","authenticated-orcid":false,"given":"Dawid","family":"Larysz","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy The Maria Sk\u0142odowska Curie Memorial Cancer Centre and Institute of Oncology  Gliwice Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-3483","authenticated-orcid":false,"given":"Bartosz","family":"Wojciechowicz","sequence":"additional","affiliation":[{"name":"Perlan Technologies Sp. z o.o. Pu\u0142awska 303 Street, 02\u2010785  Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Simon","sequence":"additional","affiliation":[{"name":"Centers for Medical Genetics GENESIS D\u0105browskiego 77A Street, 60\u2010529  Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-9336","authenticated-orcid":false,"given":"Joanna","family":"Walczak\u2010Sztulpa","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-3901","authenticated-orcid":false,"given":"Aleksander","family":"Jamsheer","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Poznan Poland"},{"name":"Centers for Medical Genetics GENESIS D\u0105browskiego 77A Street, 60\u2010529  Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"80","article-title":"Patterns of growth of the skull as revealed by vital staining","volume":"26","author":"Baer M. 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