{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:04:41Z","timestamp":1762056281066,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"MIUR-University","doi-asserted-by":"publisher","award":["Grant D1-2020","Prot. 201789LFKB"],"award-info":[{"award-number":["Grant D1-2020","Prot. 201789LFKB"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PRIN","award":["Grant D1-2020","Prot. 201789LFKB"],"award-info":[{"award-number":["Grant D1-2020","Prot. 201789LFKB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Craniosynostosis are a heterogeneous group of genetic conditions characterized by the premature fusion of the skull bones. The most common forms of craniosynostosis are Crouzon, Apert and Pfeiffer syndromes. They differ from each other in various additional clinical manifestations, e.g., syndactyly is typical of Apert and rare in Pfeiffer syndrome. Their inheritance is autosomal dominant with incomplete penetrance and one of the main genes responsible for these syndromes is FGFR2, mapped on chromosome 10, encoding fibroblast growth factor receptor 2. We report an FGFR2 gene variant in a mother and daughter who present with different clinical features of Crouzon syndrome. The daughter is more severely affected than her mother, as also verified by a careful study of the face and oral cavity. The c.1032G&gt;A transition in exon 8, already reported as a synonymous p.Ala344 = variant in Crouzon patients, also activates a new donor splice site leading to the loss of 51 nucleotides and the in-frame removal of 17 amino acids. We observed lower FGFR2 transcriptional and translational levels in the daughter compared to the mother and healthy controls. A preliminary functional assay and a molecular modeling added further details to explain the discordant phenotype of the two patients.<\/jats:p>","DOI":"10.3390\/genes13071161","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:31:14Z","timestamp":1656369074000},"page":"1161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mother and Daughter Carrying of the Same Pathogenic Variant in FGFR2 with Discordant Phenotype"],"prefix":"10.3390","volume":"13","author":[{"given":"Filomena","family":"Lo Vecchio","sequence":"first","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2242","authenticated-orcid":false,"given":"Elisabetta","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Scienze Della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Nobile","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Scienze Della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Pomponi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Pietrobono","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Scienze Della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Neri","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Scienze Della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Amenta","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettore","family":"Candida","sequence":"additional","affiliation":[{"name":"Private Practice, 00100 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9499-0556","authenticated-orcid":false,"given":"Cristina","family":"Grippaudo","sequence":"additional","affiliation":[{"name":"Dipartimento Testa Collo, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettore","family":"Lo Cascio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Vita","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Biologia Applicata, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Tiberio","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Biologia Applicata, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Arcovito","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"},{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-4936","authenticated-orcid":false,"given":"Wanda","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"},{"name":"Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Biologia Applicata, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Genuardi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"},{"name":"Dipartimento Universitario Scienze Della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-1521","authenticated-orcid":false,"given":"Pietro","family":"Chiurazzi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"},{"name":"Dipartimento Universitario Scienze Della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/ajmg.1320550422","article-title":"Genetic study of nonsyndromic coronal craniosynostosis","volume":"55","author":"Lajeunie","year":"1995","journal-title":"Am. J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/ajmg.a.32208","article-title":"A population-based study of craniosynostosis in metropolitan Atlanta, 1989\u20132003","volume":"146","author":"Boulet","year":"2008","journal-title":"Am. J. Med. Genet. 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