Publication
Title
Identification and characterization of a novel FBN1 gene variant in an extended family with variable clinical phenotype of Marfan syndrome
Author
Abstract
Marfan syndrome (MFS) is a multi-systemic autosomal dominant condition caused by mutations in the gene (FBN1) coding for fibrillin-1. Mutations have been associated with a wide range of overlapping phenotypes. Here, we report on an extended family presenting with skeletal, ocular and cardiovascular clinical features. The 37-year-old male propositus, who had chest pain, dyspnea and shortness of breath, was first diagnosed based on the revised Ghent criteria and then subjected to molecular genetic analyses. FBN1 sequencing of the proband as well as available affected family members revealed the presence of a novel variant, c.7828G>C (p.Glu2610Gln), which was not present in any of the unaffected family members. In silico analyses demonstrated that the Glu2610 residue is part of the conserved DINE motif found at the beginning of each cbEGF domain of FBN1. The substitution of Glu2610 with Gln decreased fibrillin-1 production accordingly. Despite the fact that this variation appears to be primarily responsible for the etiology of MFS in the present family, our findings suggest that variable clinical expressions of the disease phenotype should be considered critically by the physicians.
Language
English
Source (journal)
Connective tissue research. - London
Publication
London : 2019
ISSN
0300-8207
Volume/pages
60:2(2019), p. 146-154
ISI
000461646700008
Pubmed ID
29732924
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
GENOMED - Genomics in Medicine.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 26.09.2018
Last edited 15.09.2021
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