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Karola Marcinkowskiego w Poznaniu","doi-asserted-by":"publisher","award":["502-14-11261860-41259"],"award-info":[{"award-number":["502-14-11261860-41259"]}],"id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that results from pathogenic variants in the <jats:italic>EFNB1<\/jats:italic> gene. The syndrome paradoxically presents with greater severity of the symptoms in heterozygous females than hemizygous males.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We have recruited and screened a female cohort affected with CFNS. Our primary finding was the description of monozygotic twins, i.e., patients 5 and 6, discordant for the CFNS phenotype. Intriguingly, patient 5 presented classical CFNS gestalt, whereas patient 6 manifested only very subtle craniofacial features, not resembling CFNS. Besides, we have expanded the mutational spectrum of the <jats:italic>EFNB1<\/jats:italic> gene through reporting four novel pathogenic variants\u2014p.(Trp12*), p.(Cys64Phe), p.(Tyr73Met<jats:italic>fs<\/jats:italic>*86), p.(Glu210*). All those alterations were found applying either targeted NGS of a custom gene panel or PCR followed by Sanger sequencing and evaluated using in silico predictors. Lastly, we have also expanded the CFNS phenotypic spectrum by describing in patient 3\u00a0several novel features of the syndrome, such as bifid hallux, bicornuate uterus, and abnormal right ovary segmented into six parts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We have described the unreported so far differences of the clinical phenotype in the monozygotic twin patients 5 and 6 harboring an identical p.(Glu210*) variant located in the <jats:italic>EFNB1<\/jats:italic> gene. With our finding, we have pointed to an unusual phenomenon of mildly affected females with CFNS, who may not manifest features suggestive of the syndrome. Consequently, this study may be valuable for geneticists consulting patients with craniofacial disorders.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-01914-1","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T20:03:24Z","timestamp":1624737804000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-1696","authenticated-orcid":false,"given":"Ewelina","family":"Bukowska-Olech","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-5834","authenticated-orcid":false,"given":"Pawe\u0142","family":"Gawli\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jakubiuk-Tomaszuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2820-9362","authenticated-orcid":false,"given":"Maria","family":"J\u0119drzejowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-9517","authenticated-orcid":false,"given":"Ewa","family":"Obersztyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Piechota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1446-532X","authenticated-orcid":false,"given":"Marta","family":"Bielska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-3901","authenticated-orcid":false,"given":"Aleksander","family":"Jamsheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,26]]},"reference":[{"issue":"5B","key":"1914_CR1","first-page":"85","volume":"15","author":"MMJ Cohen","year":"1979","unstructured":"Cohen MMJ. 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All patients and their parents agreed to participate in this study. Written informed consent to participate in this study was provided by the participant\u2019s legal guardian\/next of kin.  Written informed consent was obtained from the minor(s)\u2019 legal guardian\/next of kin to publish any potentially identifiable images or data included in this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"ClinVar: . Face2Gene: . gnomAD: . HGMD: . OMIM: . Primer3: . Varsome: .","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Web resources"}}],"article-number":"286"}}