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Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome

Marfan syndrome (MFS) is a rare connective tissue disorder mainly due to mutations in the FBN1 gene. Great phenotypic variability is notable for age of onset, the presence and absence, and the number and the severity of the symptoms. Our team showed that FBN1 gene expression level was a good surroga...

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Autores principales: Benarroch, Louise, Aubart, Mélodie, Gross, Marie-Sylvie, Arnaud, Pauline, Hanna, Nadine, Jondeau, Guillaume, Boileau, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409622/
https://www.ncbi.nlm.nih.gov/pubmed/30754709
http://dx.doi.org/10.3390/genes10020128
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author Benarroch, Louise
Aubart, Mélodie
Gross, Marie-Sylvie
Arnaud, Pauline
Hanna, Nadine
Jondeau, Guillaume
Boileau, Catherine
author_facet Benarroch, Louise
Aubart, Mélodie
Gross, Marie-Sylvie
Arnaud, Pauline
Hanna, Nadine
Jondeau, Guillaume
Boileau, Catherine
author_sort Benarroch, Louise
collection PubMed
description Marfan syndrome (MFS) is a rare connective tissue disorder mainly due to mutations in the FBN1 gene. Great phenotypic variability is notable for age of onset, the presence and absence, and the number and the severity of the symptoms. Our team showed that FBN1 gene expression level was a good surrogate endpoint for severity of some MFS clinical features. Eight alternative transcripts are referenced for the FBN1 gene. We hypothesized that MFS clinical variability could be related to specific FBN1 isoforms. Isoform expression profiles were investigated in skin and adventitial fibroblasts from controls and MFS patients. The results of the study showed that, in skin and adventitial fibroblasts, only three isoforms were found: FBN1_001, FBN1_004, and FBN1_009. The main isoform was FBN1_001 and it was significantly reduced in skin and adventitial fibroblasts of MFS patients. The expressions of FBN1_004 and FBN1_009 isoforms were similar between controls and MFS patients. However, the expression of the three isoforms was correlated only in patients. Furthermore, their expression levels were associated with the presence of ectopia lentis in MFS patients. Therefore, our results highlight that the two minor alternatively spliced FBN1 isoforms play a possible role in the pathogenesis of the disease.
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spelling pubmed-64096222019-03-26 Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome Benarroch, Louise Aubart, Mélodie Gross, Marie-Sylvie Arnaud, Pauline Hanna, Nadine Jondeau, Guillaume Boileau, Catherine Genes (Basel) Article Marfan syndrome (MFS) is a rare connective tissue disorder mainly due to mutations in the FBN1 gene. Great phenotypic variability is notable for age of onset, the presence and absence, and the number and the severity of the symptoms. Our team showed that FBN1 gene expression level was a good surrogate endpoint for severity of some MFS clinical features. Eight alternative transcripts are referenced for the FBN1 gene. We hypothesized that MFS clinical variability could be related to specific FBN1 isoforms. Isoform expression profiles were investigated in skin and adventitial fibroblasts from controls and MFS patients. The results of the study showed that, in skin and adventitial fibroblasts, only three isoforms were found: FBN1_001, FBN1_004, and FBN1_009. The main isoform was FBN1_001 and it was significantly reduced in skin and adventitial fibroblasts of MFS patients. The expressions of FBN1_004 and FBN1_009 isoforms were similar between controls and MFS patients. However, the expression of the three isoforms was correlated only in patients. Furthermore, their expression levels were associated with the presence of ectopia lentis in MFS patients. Therefore, our results highlight that the two minor alternatively spliced FBN1 isoforms play a possible role in the pathogenesis of the disease. MDPI 2019-02-11 /pmc/articles/PMC6409622/ /pubmed/30754709 http://dx.doi.org/10.3390/genes10020128 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Benarroch, Louise
Aubart, Mélodie
Gross, Marie-Sylvie
Arnaud, Pauline
Hanna, Nadine
Jondeau, Guillaume
Boileau, Catherine
Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome
title Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome
title_full Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome
title_fullStr Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome
title_full_unstemmed Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome
title_short Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome
title_sort reference expression profile of three fbn1 transcript isoforms and their association with clinical variability in marfan syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409622/
https://www.ncbi.nlm.nih.gov/pubmed/30754709
http://dx.doi.org/10.3390/genes10020128
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