Congenital left ventricular wall defects presenting with ventricular arrhythmias: A case series.
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ABSTRACT:
SUBMITTER: Infeld M
PROVIDER: S-EPMC7573374 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Congenital left ventricular wall defects presenting with ventricular arrhythmias: A case series.
Infeld Margaret M Nicoli Charles D CD Khadanga Sherrie S VanBuren Peter P Correa de Sa Daniel D DD
HeartRhythm case reports 20200703 10
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Project description:BackgroundThe left ventricular outflow tract (LVOT) defects aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart syndrome (HLHS) represent an embryologically related group of congenital cardiovascular malformations. They are common and cause substantial morbidity and mortality. Prior evidence suggests a strong genetic component in their causation.MethodsWe selected NRG1, ERBB3, and ERBB4 of the epidermal growth factor receptor (EGFR) signaling pathway as candidate genes for investigation of association with LVOT defects based on the importance of this pathway in cardiac development and the phenotypes in knockout mouse models. Single nucleotide polymorphism (SNP) genotyping was performed on 343 affected case-parent trios of European ancestry.ResultsWe identified a specific haplotype in intron 3 of ERBB4 that was positively associated with the combined LVOT defects phenotype (p=0.0005) and in each anatomic defect AVS, COA, and HLHS separately. Mutation screening of individuals with an LVOT defect failed to identify a coding sequence or splice site change in ERBB4. RT-PCR on lymphoblastoid cells from LVOT subjects did not show altered splice variant ratios among those homozygous for the associated haplotype.ConclusionThese results suggest ERBB4 is associated with LVOT defects. Further replication will be required in separate cohorts to confirm the consistency of the observed association.
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