Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant.
FBN1
Marfan syndrome
abdominal aortic aneurysm
autosomal dominant inheritance
autosomal recessive inheritance
clinical heterogeneity
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
13
08
2018
revised:
15
10
2018
accepted:
25
10
2018
pubmed:
30
11
2018
medline:
12
4
2019
entrez:
29
11
2018
Statut:
ppublish
Résumé
Pathogenic variants in FBN1 cause autosomal dominant Marfan syndrome but can also be found in patients presenting with apparently isolated features of Marfan syndrome. Moreover, several families with autosomal recessive Marfan syndrome caused by pathogenic variants in FBN1 have been described. The aim of this report was to underline the clinical variability that can be associated with the pathogenic variant c.1453C>T, p.(Arg485Cys) in FBN1. We provide the clinical details of two autosomal dominant families with this specific FBN1 variant, which was previously associated with autosomal recessive Marfan syndrome. Clinical data of 14 individuals carrying this variant from these two families were collected retrospectively. In both families, the diagnosis of autosomal dominant Marfan syndrome was established based on the characteristics of the variant and the phenotype which includes aortic aneurysms and dissections. Of interest, in one of the families, multiple relatives were diagnosed with early onset abdominal aortic aneurysms. In conclusion, FBN1 variant c.1453C>T, p.(Arg485Cys) is a pathogenic variant that can cause autosomal dominant Marfan syndrome characterized by a high degree of clinical variability and apparently isolated early onset familial abdominal aortic aneurysms.
Sections du résumé
BACKGROUND
Pathogenic variants in FBN1 cause autosomal dominant Marfan syndrome but can also be found in patients presenting with apparently isolated features of Marfan syndrome. Moreover, several families with autosomal recessive Marfan syndrome caused by pathogenic variants in FBN1 have been described. The aim of this report was to underline the clinical variability that can be associated with the pathogenic variant c.1453C>T, p.(Arg485Cys) in FBN1.
METHODS
We provide the clinical details of two autosomal dominant families with this specific FBN1 variant, which was previously associated with autosomal recessive Marfan syndrome.
RESULTS
Clinical data of 14 individuals carrying this variant from these two families were collected retrospectively. In both families, the diagnosis of autosomal dominant Marfan syndrome was established based on the characteristics of the variant and the phenotype which includes aortic aneurysms and dissections. Of interest, in one of the families, multiple relatives were diagnosed with early onset abdominal aortic aneurysms.
CONCLUSION
In conclusion, FBN1 variant c.1453C>T, p.(Arg485Cys) is a pathogenic variant that can cause autosomal dominant Marfan syndrome characterized by a high degree of clinical variability and apparently isolated early onset familial abdominal aortic aneurysms.
Identifiants
pubmed: 30485715
doi: 10.1002/mgg3.518
pmc: PMC6393656
doi:
Substances chimiques
FBN1 protein, human
0
Fibrillin-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00518Informations de copyright
© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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