Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome: A 10-year single center experience

Autor: Valentina Ferradini, Giovanni Ruvolo, Laura Gigante, Federica Sangiuolo, Serena Luciano, Liliana Mannucci, Chiara Conte, Nunzia Piumelli, Francesco Brancati, Giuseppe Novelli, Leila B. Salehi, Giuliana Longo
Rok vydání: 2019
Předmět:
0301 basic medicine
Marfan syndrome
Nosology
Male
Fibrillin-1
Clinical Biochemistry
DNA Mutational Analysis
Single Center
medicine.disease_cause
Biochemistry
Marfan Syndrome
Cohort Studies
0302 clinical medicine
skin and connective tissue diseases
Child
Aortic dissection
Mutation
High-Throughput Nucleotide Sequencing
General Medicine
Middle Aged
FBN1
Gene variants
MFS
NGS
Italy
030220 oncology & carcinogenesis
Child
Preschool
Cohort
Female
musculoskeletal diseases
Adult
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
Adolescent
macromolecular substances
03 medical and health sciences
Young Adult
Internal medicine
medicine
Humans
cardiovascular diseases
Gene
business.industry
Biochemistry (medical)
medicine.disease
030104 developmental biology
Settore MED/03 - Genetica Medica
Mutation testing
business
Zdroj: Clinica chimica acta; international journal of clinical chemistry. 501
ISSN: 1873-3492
Popis: 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.
Databáze: OpenAIRE
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