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Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene

Hypertrophic cardiomyopathy (HCM) is a type of primary cardiomyopathy with genetic etiology, and it carries a high risk of diastolic dysfunction, heart failure, and malignant arrhythmias. We reported the first familial HCM in China, caused by a novel FLNC splicing mutation. We performed duo exome se...

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Autores principales: Huang, Chunhui, Zheng, Yonghong, Zhang, Wei, Chen, Zhigang, Huang, Zhixin, Fang, Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251305/
https://www.ncbi.nlm.nih.gov/pubmed/35795207
http://dx.doi.org/10.3389/fgene.2022.894791
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author Huang, Chunhui
Zheng, Yonghong
Zhang, Wei
Chen, Zhigang
Huang, Zhixin
Fang, Yuan
author_facet Huang, Chunhui
Zheng, Yonghong
Zhang, Wei
Chen, Zhigang
Huang, Zhixin
Fang, Yuan
author_sort Huang, Chunhui
collection PubMed
description Hypertrophic cardiomyopathy (HCM) is a type of primary cardiomyopathy with genetic etiology, and it carries a high risk of diastolic dysfunction, heart failure, and malignant arrhythmias. We reported the first familial HCM in China, caused by a novel FLNC splicing mutation. We performed duo exome sequencing (ES) to examine the genome of the proband and his mother. For 10 days, a 15-year-old boy was presented to our hospital due to non–exercise-associated chest tightness and asthma. He was diagnosed with HCM [end-diastolic interventricular septal thickness was about 18 mm by transthoracic echocardiography (TTE)]. His mother and sister performed TTE to screen familial cardiomyopathy, which revealed hypertrophic cardiomyopathy only in the proband’s mother. In ES of the mother–son duo, we identified a novel heterozygous mutation of the FLNC gene (chr7:128492808, NM_001127487, c.5905+2T>C, rs1808874360) as the candidate cause of autosomal dominant HCM. Sanger sequencing confirmed this novel mutation in the proband and his mother but absent in the proband’s sister. The potential impact of the novel mutation was predicted by MutationTaster, dbscSNV_ADA_SCORE, dbscSNV_RF_SCORE, CADD_phred, PhyloP20way_mammalian, PhyloP100way_vertebrate, SiPhy_29way_logOdds, and GERP++_RS software. After the administration of furosemide, spironolactone, and metoprolol, the proband’s heart function was improved, and symptoms were alleviated. We presented the first familial HCM caused by a novel FLNC splicing mutation via exome sequencing in China. Therefore, it is necessary that familial screening for patients with HCM should be performed for the early detection of HCM intervention in malignant cardiac events in advance and block genes.
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spelling pubmed-92513052022-07-05 Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene Huang, Chunhui Zheng, Yonghong Zhang, Wei Chen, Zhigang Huang, Zhixin Fang, Yuan Front Genet Genetics Hypertrophic cardiomyopathy (HCM) is a type of primary cardiomyopathy with genetic etiology, and it carries a high risk of diastolic dysfunction, heart failure, and malignant arrhythmias. We reported the first familial HCM in China, caused by a novel FLNC splicing mutation. We performed duo exome sequencing (ES) to examine the genome of the proband and his mother. For 10 days, a 15-year-old boy was presented to our hospital due to non–exercise-associated chest tightness and asthma. He was diagnosed with HCM [end-diastolic interventricular septal thickness was about 18 mm by transthoracic echocardiography (TTE)]. His mother and sister performed TTE to screen familial cardiomyopathy, which revealed hypertrophic cardiomyopathy only in the proband’s mother. In ES of the mother–son duo, we identified a novel heterozygous mutation of the FLNC gene (chr7:128492808, NM_001127487, c.5905+2T>C, rs1808874360) as the candidate cause of autosomal dominant HCM. Sanger sequencing confirmed this novel mutation in the proband and his mother but absent in the proband’s sister. The potential impact of the novel mutation was predicted by MutationTaster, dbscSNV_ADA_SCORE, dbscSNV_RF_SCORE, CADD_phred, PhyloP20way_mammalian, PhyloP100way_vertebrate, SiPhy_29way_logOdds, and GERP++_RS software. After the administration of furosemide, spironolactone, and metoprolol, the proband’s heart function was improved, and symptoms were alleviated. We presented the first familial HCM caused by a novel FLNC splicing mutation via exome sequencing in China. Therefore, it is necessary that familial screening for patients with HCM should be performed for the early detection of HCM intervention in malignant cardiac events in advance and block genes. Frontiers Media S.A. 2022-06-20 /pmc/articles/PMC9251305/ /pubmed/35795207 http://dx.doi.org/10.3389/fgene.2022.894791 Text en Copyright © 2022 Huang, Zheng, Zhang, Chen, Huang and Fang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Huang, Chunhui
Zheng, Yonghong
Zhang, Wei
Chen, Zhigang
Huang, Zhixin
Fang, Yuan
Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
title Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
title_full Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
title_fullStr Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
title_full_unstemmed Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
title_short Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
title_sort case report: a chinese family of hypertrophic cardiomyopathy caused by a novel splicing mutation in the flnc gene
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251305/
https://www.ncbi.nlm.nih.gov/pubmed/35795207
http://dx.doi.org/10.3389/fgene.2022.894791
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