Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1161 |
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| author | Filomena Lo Vecchio Elisabetta Tabolacci Veronica Nobile Maria Grazia Pomponi Roberta Pietrobono Giovanni Neri Simona Amenta Ettore Candida Cristina Grippaudo Ettore Lo Cascio Alessia Vita Federica Tiberio Alessandro Arcovito Wanda Lattanzi Maurizio Genuardi Pietro Chiurazzi |
| author_facet | Filomena Lo Vecchio Elisabetta Tabolacci Veronica Nobile Maria Grazia Pomponi Roberta Pietrobono Giovanni Neri Simona Amenta Ettore Candida Cristina Grippaudo Ettore Lo Cascio Alessia Vita Federica Tiberio Alessandro Arcovito Wanda Lattanzi Maurizio Genuardi Pietro Chiurazzi |
| author_sort | Filomena Lo Vecchio |
| collection | DOAJ |
| description | 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 <i>FGFR2</i>, mapped on chromosome 10, encoding fibroblast growth factor receptor 2. We report an <i>FGFR2</i> 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>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 <i>FGFR2</i> 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. |
| first_indexed | 2024-03-09T03:23:32Z |
| format | Article |
| id | doaj.art-6f0da198780842458e8574610bc8fd16 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T03:23:32Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-6f0da198780842458e8574610bc8fd162023-12-03T15:05:42ZengMDPI AGGenes2073-44252022-06-01137116110.3390/genes13071161Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant PhenotypeFilomena Lo Vecchio0Elisabetta Tabolacci1Veronica Nobile2Maria Grazia Pomponi3Roberta Pietrobono4Giovanni Neri5Simona Amenta6Ettore Candida7Cristina Grippaudo8Ettore Lo Cascio9Alessia Vita10Federica Tiberio11Alessandro Arcovito12Wanda Lattanzi13Maurizio Genuardi14Pietro Chiurazzi15UOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyDipartimento Universitario Scienze Della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyDipartimento Universitario Scienze Della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyUOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyDipartimento Universitario Scienze Della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyDipartimento Universitario Scienze Della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyUOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyPrivate Practice, 00100 Rome, ItalyDipartimento Testa Collo, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Roma, ItalyDipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Biologia Applicata, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Roma, ItalyDipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Biologia Applicata, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Roma, ItalyFondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyFondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyUOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyUOC Genetica Medica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Roma, ItalyCraniosynostosis 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 <i>FGFR2</i>, mapped on chromosome 10, encoding fibroblast growth factor receptor 2. We report an <i>FGFR2</i> 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>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 <i>FGFR2</i> 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.https://www.mdpi.com/2073-4425/13/7/1161<i>FGFR2</i>craniosynostosissynonymous variantclinical phenotypegenetic medicineneurosurgery |
| spellingShingle | Filomena Lo Vecchio Elisabetta Tabolacci Veronica Nobile Maria Grazia Pomponi Roberta Pietrobono Giovanni Neri Simona Amenta Ettore Candida Cristina Grippaudo Ettore Lo Cascio Alessia Vita Federica Tiberio Alessandro Arcovito Wanda Lattanzi Maurizio Genuardi Pietro Chiurazzi Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype Genes <i>FGFR2</i> craniosynostosis synonymous variant clinical phenotype genetic medicine neurosurgery |
| title | Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype |
| title_full | Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype |
| title_fullStr | Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype |
| title_full_unstemmed | Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype |
| title_short | Mother and Daughter Carrying of the Same Pathogenic Variant in <i>FGFR2</i> with Discordant Phenotype |
| title_sort | mother and daughter carrying of the same pathogenic variant in i fgfr2 i with discordant phenotype |
| topic | <i>FGFR2</i> craniosynostosis synonymous variant clinical phenotype genetic medicine neurosurgery |
| url | https://www.mdpi.com/2073-4425/13/7/1161 |
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