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Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients
Filamin C is a protein specifically expressed in myocytes and cardiomyocytes and is involved in several biological functions, including sarcomere contractile activity, signaling, cellular adhesion, and repair. FLNC variants are associated with different disorders ranging from striated muscle (myofib...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604120/ https://www.ncbi.nlm.nih.gov/pubmed/36286284 http://dx.doi.org/10.3390/jcdd9100332 |
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author | Baban, Anwar Alesi, Viola Magliozzi, Monia Parlapiano, Giovanni Genovese, Silvia Cicenia, Marianna Loddo, Sara Lodato, Valentina Di Chiara, Luca Fattori, Fabiana D’Amico, Adele Francalanci, Paola Amodeo, Antonio Novelli, Antonio Drago, Fabrizio |
author_facet | Baban, Anwar Alesi, Viola Magliozzi, Monia Parlapiano, Giovanni Genovese, Silvia Cicenia, Marianna Loddo, Sara Lodato, Valentina Di Chiara, Luca Fattori, Fabiana D’Amico, Adele Francalanci, Paola Amodeo, Antonio Novelli, Antonio Drago, Fabrizio |
author_sort | Baban, Anwar |
collection | PubMed |
description | Filamin C is a protein specifically expressed in myocytes and cardiomyocytes and is involved in several biological functions, including sarcomere contractile activity, signaling, cellular adhesion, and repair. FLNC variants are associated with different disorders ranging from striated muscle (myofibrillar distal or proximal) myopathy to cardiomyopathies (CMPs) (restrictive, hypertrophic, and dilated), or both. The outcome depends on functional consequences of the detected variants, which result either in FLNC haploinsufficiency or in an aberrant protein, the latter affecting sarcomere structure leading to protein aggregates. Cardiac manifestations of filaminopathies are most often described as adult onset CMPs and limited reports are available in children or on other cardiac spectrums (congenital heart defects—CHDs, or arrhythmias). Here we report on 13 variants in 14 children (2.8%) out of 500 pediatric patients with early-onset different cardiac features ranging from CMP to arrhythmias and CHDs. In one patient, we identified a deletion encompassing FLNC detected by microarray, which was overlooked by next generation sequencing. We established a potential genotype–phenotype correlation of the p.Ala1186Val variant in severe and early-onset restrictive cardiomyopathy (RCM) associated with a limb-girdle defect (two new patients in addition to the five reported in the literature). Moreover, in three patients (21%), we identified a relatively frequent finding of long QT syndrome (LQTS) associated with RCM (n = 2) and a hypertrabeculated left ventricle (n = 1). RCM and LQTS in children might represent a specific red flag for FLNC variants. Further studies are warranted in pediatric cohorts to delineate potential expanding phenotypes related to FLNC. |
format | Online Article Text |
id | pubmed-9604120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96041202022-10-27 Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients Baban, Anwar Alesi, Viola Magliozzi, Monia Parlapiano, Giovanni Genovese, Silvia Cicenia, Marianna Loddo, Sara Lodato, Valentina Di Chiara, Luca Fattori, Fabiana D’Amico, Adele Francalanci, Paola Amodeo, Antonio Novelli, Antonio Drago, Fabrizio J Cardiovasc Dev Dis Article Filamin C is a protein specifically expressed in myocytes and cardiomyocytes and is involved in several biological functions, including sarcomere contractile activity, signaling, cellular adhesion, and repair. FLNC variants are associated with different disorders ranging from striated muscle (myofibrillar distal or proximal) myopathy to cardiomyopathies (CMPs) (restrictive, hypertrophic, and dilated), or both. The outcome depends on functional consequences of the detected variants, which result either in FLNC haploinsufficiency or in an aberrant protein, the latter affecting sarcomere structure leading to protein aggregates. Cardiac manifestations of filaminopathies are most often described as adult onset CMPs and limited reports are available in children or on other cardiac spectrums (congenital heart defects—CHDs, or arrhythmias). Here we report on 13 variants in 14 children (2.8%) out of 500 pediatric patients with early-onset different cardiac features ranging from CMP to arrhythmias and CHDs. In one patient, we identified a deletion encompassing FLNC detected by microarray, which was overlooked by next generation sequencing. We established a potential genotype–phenotype correlation of the p.Ala1186Val variant in severe and early-onset restrictive cardiomyopathy (RCM) associated with a limb-girdle defect (two new patients in addition to the five reported in the literature). Moreover, in three patients (21%), we identified a relatively frequent finding of long QT syndrome (LQTS) associated with RCM (n = 2) and a hypertrabeculated left ventricle (n = 1). RCM and LQTS in children might represent a specific red flag for FLNC variants. Further studies are warranted in pediatric cohorts to delineate potential expanding phenotypes related to FLNC. MDPI 2022-09-30 /pmc/articles/PMC9604120/ /pubmed/36286284 http://dx.doi.org/10.3390/jcdd9100332 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Baban, Anwar Alesi, Viola Magliozzi, Monia Parlapiano, Giovanni Genovese, Silvia Cicenia, Marianna Loddo, Sara Lodato, Valentina Di Chiara, Luca Fattori, Fabiana D’Amico, Adele Francalanci, Paola Amodeo, Antonio Novelli, Antonio Drago, Fabrizio Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients |
title | Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients |
title_full | Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients |
title_fullStr | Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients |
title_full_unstemmed | Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients |
title_short | Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients |
title_sort | cardiovascular involvement in pediatric flnc variants: a case series of fourteen patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604120/ https://www.ncbi.nlm.nih.gov/pubmed/36286284 http://dx.doi.org/10.3390/jcdd9100332 |
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