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Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy

Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular...

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Autores principales: Szulik, Marta W., Reyes-Múgica, Miguel, Marker, Daniel F., Gomez, Ana M., Zinn, Matthew D., Walsh, Leslie K., Ochoa, Juan Pablo, Franklin, Sarah, Ghaloul-Gonzalez, Lina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048717/
https://www.ncbi.nlm.nih.gov/pubmed/36980931
http://dx.doi.org/10.3390/genes14030659
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author Szulik, Marta W.
Reyes-Múgica, Miguel
Marker, Daniel F.
Gomez, Ana M.
Zinn, Matthew D.
Walsh, Leslie K.
Ochoa, Juan Pablo
Franklin, Sarah
Ghaloul-Gonzalez, Lina
author_facet Szulik, Marta W.
Reyes-Múgica, Miguel
Marker, Daniel F.
Gomez, Ana M.
Zinn, Matthew D.
Walsh, Leslie K.
Ochoa, Juan Pablo
Franklin, Sarah
Ghaloul-Gonzalez, Lina
author_sort Szulik, Marta W.
collection PubMed
description Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular heart failure carrying a truncating homozygous MYBPC3 variant c.1224-52G>A (IVS13-52G>A) and a novel homozygous variant (c.302A>G; p.Asn101Ser) in the SMYD1 gene. The second patient, the proband’s sibling, is a male infant diagnosed with hypertrophic cardiomyopathy and carries the same homozygous MYBPC3 variant. While this specific MYBPC3 variant (c.1224-52G>A, IVS13-52G>A) has been previously reported to be associated with adult-onset hypertrophic cardiomyopathy, this is the first report linking it to infantile cardiomyopathy. In addition, this work describes, for the first time, a novel SMYD1 variant (c.302A>G; p.Asn101Ser) that has never been reported. We performed a histopathological evaluation of tissues collected from both probands and show that these variants lead to myofibrillar disarray, reduced and irregular mitochondrial cristae and cardiac fibrosis. Together, these results provide critical insight into the molecular functionality of these genes in human cardiac physiology.
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spelling pubmed-100487172023-03-29 Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy Szulik, Marta W. Reyes-Múgica, Miguel Marker, Daniel F. Gomez, Ana M. Zinn, Matthew D. Walsh, Leslie K. Ochoa, Juan Pablo Franklin, Sarah Ghaloul-Gonzalez, Lina Genes (Basel) Article Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular heart failure carrying a truncating homozygous MYBPC3 variant c.1224-52G>A (IVS13-52G>A) and a novel homozygous variant (c.302A>G; p.Asn101Ser) in the SMYD1 gene. The second patient, the proband’s sibling, is a male infant diagnosed with hypertrophic cardiomyopathy and carries the same homozygous MYBPC3 variant. While this specific MYBPC3 variant (c.1224-52G>A, IVS13-52G>A) has been previously reported to be associated with adult-onset hypertrophic cardiomyopathy, this is the first report linking it to infantile cardiomyopathy. In addition, this work describes, for the first time, a novel SMYD1 variant (c.302A>G; p.Asn101Ser) that has never been reported. We performed a histopathological evaluation of tissues collected from both probands and show that these variants lead to myofibrillar disarray, reduced and irregular mitochondrial cristae and cardiac fibrosis. Together, these results provide critical insight into the molecular functionality of these genes in human cardiac physiology. MDPI 2023-03-06 /pmc/articles/PMC10048717/ /pubmed/36980931 http://dx.doi.org/10.3390/genes14030659 Text en © 2023 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
Szulik, Marta W.
Reyes-Múgica, Miguel
Marker, Daniel F.
Gomez, Ana M.
Zinn, Matthew D.
Walsh, Leslie K.
Ochoa, Juan Pablo
Franklin, Sarah
Ghaloul-Gonzalez, Lina
Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy
title Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy
title_full Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy
title_fullStr Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy
title_full_unstemmed Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy
title_short Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy
title_sort identification of two homozygous variants in mybpc3 and smyd1 genes associated with severe infantile cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048717/
https://www.ncbi.nlm.nih.gov/pubmed/36980931
http://dx.doi.org/10.3390/genes14030659
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