A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement
Abstract Background Vascular Ehlers–Danlos syndrome (vEDS) is a heritable connective tissue disorder caused by defects in the type III collagen protein. It is generally considered the most severe form of Ehlers–Danlos syndrome (EDS) due to an increased risk of spontaneous artery or organ rupture. vE...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-09-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1753 |
| _version_ | 1818576500410023936 |
|---|---|
| author | Federica Ruscitti Lucia Trevisan Giulia Rosti Fabio Gotta Annalia Cianflone Alessandro Geroldi Paola Origone Anna Pichiecchio Simona Viglio Maria Iascone Paola Mandich |
| author_facet | Federica Ruscitti Lucia Trevisan Giulia Rosti Fabio Gotta Annalia Cianflone Alessandro Geroldi Paola Origone Anna Pichiecchio Simona Viglio Maria Iascone Paola Mandich |
| author_sort | Federica Ruscitti |
| collection | DOAJ |
| description | Abstract Background Vascular Ehlers–Danlos syndrome (vEDS) is a heritable connective tissue disorder caused by defects in the type III collagen protein. It is generally considered the most severe form of Ehlers–Danlos syndrome (EDS) due to an increased risk of spontaneous artery or organ rupture. vEDS has an extremely heterogeneous presentation and muscle rupture is considered a minor diagnostic criterium. Methods A patient with a long history of inconclusive examinations and investigations was referred to our unit. The clinical picture was mainly characterized by muscle ruptures, whereas the cardiovascular involvement was limited to mitral regurgitation. We performed a panel analysis of genes associated with inheritable heart diseases using the TruSight Cardio kit (Illumina). A skin biopsy was then performed for functional studies to analyze the different forms of collagen molecules produced in vitro by cutaneous fibroblasts. Results The patient presented the novel variant c.3478A>G (p.Ile1160Val) in COL3A1 (NM_000090.3), whose pathogenicity was supported by biochemical analysis of type III collagen. Conclusion In this report, we describe a case of vEDS with predominant and severe musculoskeletal involvement. Our findings provide insight into genetic variants and clinical expression of vEDS, broadening the clinical scenario of the syndrome. |
| first_indexed | 2024-12-16T06:15:00Z |
| format | Article |
| id | doaj.art-a99c5fcb34744210b551b9bbcb913e1a |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-16T06:15:00Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-a99c5fcb34744210b551b9bbcb913e1a2022-12-21T22:41:17ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-09-0199n/an/a10.1002/mgg3.1753A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvementFederica Ruscitti0Lucia Trevisan1Giulia Rosti2Fabio Gotta3Annalia Cianflone4Alessandro Geroldi5Paola Origone6Anna Pichiecchio7Simona Viglio8Maria Iascone9Paola Mandich10DINOGMI Department University of Genoa Genoa ItalyDINOGMI Department University of Genoa Genoa ItalyDINOGMI Department University of Genoa Genoa ItalyMedical Genetics Unit IRCCS Ospedale Policlinico San Martino Genoa ItalyDINOGMI Department University of Genoa Genoa ItalyDINOGMI Department University of Genoa Genoa ItalyDINOGMI Department University of Genoa Genoa ItalyNeuroradiology Department IRCCS Mondino Foundation Pavia ItalyBiochemistry Unit Department of Molecular Medicine University of Pavia Pavia ItalyMedical Genetics Laboratory Hospital Papa Giovanni XXIII Bergamo ItalyDINOGMI Department University of Genoa Genoa ItalyAbstract Background Vascular Ehlers–Danlos syndrome (vEDS) is a heritable connective tissue disorder caused by defects in the type III collagen protein. It is generally considered the most severe form of Ehlers–Danlos syndrome (EDS) due to an increased risk of spontaneous artery or organ rupture. vEDS has an extremely heterogeneous presentation and muscle rupture is considered a minor diagnostic criterium. Methods A patient with a long history of inconclusive examinations and investigations was referred to our unit. The clinical picture was mainly characterized by muscle ruptures, whereas the cardiovascular involvement was limited to mitral regurgitation. We performed a panel analysis of genes associated with inheritable heart diseases using the TruSight Cardio kit (Illumina). A skin biopsy was then performed for functional studies to analyze the different forms of collagen molecules produced in vitro by cutaneous fibroblasts. Results The patient presented the novel variant c.3478A>G (p.Ile1160Val) in COL3A1 (NM_000090.3), whose pathogenicity was supported by biochemical analysis of type III collagen. Conclusion In this report, we describe a case of vEDS with predominant and severe musculoskeletal involvement. Our findings provide insight into genetic variants and clinical expression of vEDS, broadening the clinical scenario of the syndrome.https://doi.org/10.1002/mgg3.1753COL3A1musculoskeletal involvementNGSvEDS |
| spellingShingle | Federica Ruscitti Lucia Trevisan Giulia Rosti Fabio Gotta Annalia Cianflone Alessandro Geroldi Paola Origone Anna Pichiecchio Simona Viglio Maria Iascone Paola Mandich A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement Molecular Genetics & Genomic Medicine COL3A1 musculoskeletal involvement NGS vEDS |
| title | A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement |
| title_full | A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement |
| title_fullStr | A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement |
| title_full_unstemmed | A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement |
| title_short | A novel mutation in COL3A1 associates to vascular Ehlers–Danlos syndrome with predominant musculoskeletal involvement |
| title_sort | novel mutation in col3a1 associates to vascular ehlers danlos syndrome with predominant musculoskeletal involvement |
| topic | COL3A1 musculoskeletal involvement NGS vEDS |
| url | https://doi.org/10.1002/mgg3.1753 |
| work_keys_str_mv | AT federicaruscitti anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT luciatrevisan anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT giuliarosti anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT fabiogotta anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT annaliacianflone anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT alessandrogeroldi anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT paolaorigone anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT annapichiecchio anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT simonaviglio anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT mariaiascone anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT paolamandich anovelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT federicaruscitti novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT luciatrevisan novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT giuliarosti novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT fabiogotta novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT annaliacianflone novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT alessandrogeroldi novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT paolaorigone novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT annapichiecchio novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT simonaviglio novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT mariaiascone novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement AT paolamandich novelmutationincol3a1associatestovascularehlersdanlossyndromewithpredominantmusculoskeletalinvolvement |