A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome
Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by hyperplastic polyps in the upper and lower gastrointestinal (GI) tract with a high risk of developing GI cancers. We have described a three-generation Italian family with all the spectrum of <i>SMAD4</i>...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/11/2684 |
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| author | Caterina Micolonghi Maria Piane Aldo Germani Soha Sadeghi Fabio Libi Camilla Savio Marco Fabiani Rita Mancini Danilo Ranieri Antonio Pizzuti Vito Domenico Corleto Pasquale Parisi Vincenzo Visco Giovanni Di Nardo Simona Petrucci |
| author_facet | Caterina Micolonghi Maria Piane Aldo Germani Soha Sadeghi Fabio Libi Camilla Savio Marco Fabiani Rita Mancini Danilo Ranieri Antonio Pizzuti Vito Domenico Corleto Pasquale Parisi Vincenzo Visco Giovanni Di Nardo Simona Petrucci |
| author_sort | Caterina Micolonghi |
| collection | DOAJ |
| description | Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by hyperplastic polyps in the upper and lower gastrointestinal (GI) tract with a high risk of developing GI cancers. We have described a three-generation Italian family with all the spectrum of <i>SMAD4</i> phenotype. A multigene panel test was performed on the genomic DNA of the proband by next-generation sequencing, including genes related to hereditary GI tumor syndromes. Molecular analysis revealed the presence of the c.1140-2A>G substitution in the <i>SMAD4</i> gene, a novel splice variant that has never been described before. Our family is remarkable in that it illustrates the variable expressivity of the <i>SMAD4</i> phenotype within the same family. The possibility of phenotype variability should also be considered within family members carrying the same mutation. In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life. |
| first_indexed | 2024-03-09T19:09:28Z |
| format | Article |
| id | doaj.art-8a86928455a94d798062d85bc1dfc421 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T19:09:28Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-8a86928455a94d798062d85bc1dfc4212023-11-24T04:19:18ZengMDPI AGDiagnostics2075-44182022-11-011211268410.3390/diagnostics12112684A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis SyndromeCaterina Micolonghi0Maria Piane1Aldo Germani2Soha Sadeghi3Fabio Libi4Camilla Savio5Marco Fabiani6Rita Mancini7Danilo Ranieri8Antonio Pizzuti9Vito Domenico Corleto10Pasquale Parisi11Vincenzo Visco12Giovanni Di Nardo13Simona Petrucci14Department of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00161 Rome, ItalyS. Andrea University Hospital, 00189 Rome, ItalyS. Andrea University Hospital, 00189 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00161 Rome, ItalyS. Andrea University Hospital, 00189 Rome, ItalyS. Andrea University Hospital, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, ItalyS. Andrea University Hospital, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, ItalyJuvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by hyperplastic polyps in the upper and lower gastrointestinal (GI) tract with a high risk of developing GI cancers. We have described a three-generation Italian family with all the spectrum of <i>SMAD4</i> phenotype. A multigene panel test was performed on the genomic DNA of the proband by next-generation sequencing, including genes related to hereditary GI tumor syndromes. Molecular analysis revealed the presence of the c.1140-2A>G substitution in the <i>SMAD4</i> gene, a novel splice variant that has never been described before. Our family is remarkable in that it illustrates the variable expressivity of the <i>SMAD4</i> phenotype within the same family. The possibility of phenotype variability should also be considered within family members carrying the same mutation. In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life.https://www.mdpi.com/2075-4418/12/11/2684juvenile polyposis syndrome<i>SMAD4</i>splice site variant |
| spellingShingle | Caterina Micolonghi Maria Piane Aldo Germani Soha Sadeghi Fabio Libi Camilla Savio Marco Fabiani Rita Mancini Danilo Ranieri Antonio Pizzuti Vito Domenico Corleto Pasquale Parisi Vincenzo Visco Giovanni Di Nardo Simona Petrucci A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome Diagnostics juvenile polyposis syndrome <i>SMAD4</i> splice site variant |
| title | A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome |
| title_full | A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome |
| title_fullStr | A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome |
| title_full_unstemmed | A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome |
| title_short | A New <i>SMAD4</i> Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome |
| title_sort | new i smad4 i splice site variant in a three generation italian family with juvenile polyposis syndrome |
| topic | juvenile polyposis syndrome <i>SMAD4</i> splice site variant |
| url | https://www.mdpi.com/2075-4418/12/11/2684 |
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