Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome : A 10-year single center experience
Copyright © 2019 Elsevier B.V. All rights reserved..
BACKGROUND: Marfan Syndrome (MFS) is a chronic, life-threatening, autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene, coding for fibrillin-1. All organ systems may be affected, but particularly the cardiovascular system, eyes, and skeleton. Mortality generally results from cardiovascular complications, mainly aortic dissection. Currently, the diagnosis of MFS is based on the revised Ghent nosology. Molecular analysis of the FBN1 gene reduces diagnostic uncertainty in patients with suspected MFS or MFS-related disorders (MFS-RD). To date, more than 2700 FBN1 mutations are known.
METHODS: Using Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome.
RESULTS: An FBN1 variant was identified in 107/124 (86.3%) patients, including 48 novel variants (46 pathogenic/likely pathogenic, 2 VUS). A pathogenic/likely pathogenic variant was detected in 90/101 (89.1%) MFS patients. Our approach allowed early diagnosis for 10 young patients (age 3-19 years) with suspected MFS.
CONCLUSIONS: This study broadens the mutation spectrum of FBN1, providing a full update of the molecular basis of MFS in Italy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:501 |
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| Enthalten in: |
Clinica chimica acta; international journal of clinical chemistry - 501(2020) vom: 15. Feb., Seite 154-164 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mannucci, Liliana [VerfasserIn] |
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| Links: |
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| Themen: |
FBN1 |
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| Anmerkungen: |
Date Completed 29.07.2020 Date Revised 29.07.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cca.2019.10.037 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30334024X |
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| 100 | 1 | |a Mannucci, Liliana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome |b A 10-year single center experience |
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| 500 | |a Date Revised 29.07.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Marfan Syndrome (MFS) is a chronic, life-threatening, autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene, coding for fibrillin-1. All organ systems may be affected, but particularly the cardiovascular system, eyes, and skeleton. Mortality generally results from cardiovascular complications, mainly aortic dissection. Currently, the diagnosis of MFS is based on the revised Ghent nosology. Molecular analysis of the FBN1 gene reduces diagnostic uncertainty in patients with suspected MFS or MFS-related disorders (MFS-RD). To date, more than 2700 FBN1 mutations are known | ||
| 520 | |a METHODS: Using Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome | ||
| 520 | |a RESULTS: An FBN1 variant was identified in 107/124 (86.3%) patients, including 48 novel variants (46 pathogenic/likely pathogenic, 2 VUS). A pathogenic/likely pathogenic variant was detected in 90/101 (89.1%) MFS patients. Our approach allowed early diagnosis for 10 young patients (age 3-19 years) with suspected MFS | ||
| 520 | |a CONCLUSIONS: This study broadens the mutation spectrum of FBN1, providing a full update of the molecular basis of MFS in Italy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a FBN1 | |
| 650 | 4 | |a Gene variants | |
| 650 | 4 | |a MFS | |
| 650 | 4 | |a Marfan syndrome | |
| 650 | 4 | |a NGS | |
| 650 | 7 | |a FBN1 protein, human |2 NLM | |
| 650 | 7 | |a Fibrillin-1 |2 NLM | |
| 700 | 1 | |a Luciano, Serena |e verfasserin |4 aut | |
| 700 | 1 | |a Salehi, Leila B |e verfasserin |4 aut | |
| 700 | 1 | |a Gigante, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Conte, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Longo, Giuliana |e verfasserin |4 aut | |
| 700 | 1 | |a Ferradini, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Piumelli, Nunzia |e verfasserin |4 aut | |
| 700 | 1 | |a Brancati, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Ruvolo, Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a Novelli, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Sangiuolo, Federica |e verfasserin |4 aut | |
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