2020
DOI: 10.1002/mgg3.1150
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Potential digenic inheritance of familial hypertrophic cardiomyopathy identified by whole‐exome sequencing

Abstract: Background The aim of this study was to identify the genetic causes of patients with hypertrophic cardiomyopathy (HCM) within a family. Most of the previous studies found point mutations as the genetic causes for HCM, whole‐gene deletion was rarely reported. Methods Although, clinical genetic testing has been widely used for identifying variants in HCM patients, structural variations are understudied, partly owing to the inadequacy of the available methodology. In the present study, whole‐exome sequencing (WES… Show more

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Cited by 4 publications
(4 citation statements)
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“…The fact that the TMPO variant p.(Leu124Phe) could be a genetic contributor to DCM, is supported by the absence of additional gene variants identified by exome sequencing in Patient 6. However, since severe phenotype in newborn patients is frequently due to co-dominance of genes, as previously reported both in DCM and HCM [36][37][38], we suggest that the extreme severity and precocity of the phenotype for patient 5 (death at 2.5 months) may be due to a cumulative effect of probably genetic and/or non-genetic factors yet unidentified to date despite exome sequencing.…”
Section: Combined Phenotyping and Gene Panel Sequencing Approaches Su...supporting
confidence: 68%
“…The fact that the TMPO variant p.(Leu124Phe) could be a genetic contributor to DCM, is supported by the absence of additional gene variants identified by exome sequencing in Patient 6. However, since severe phenotype in newborn patients is frequently due to co-dominance of genes, as previously reported both in DCM and HCM [36][37][38], we suggest that the extreme severity and precocity of the phenotype for patient 5 (death at 2.5 months) may be due to a cumulative effect of probably genetic and/or non-genetic factors yet unidentified to date despite exome sequencing.…”
Section: Combined Phenotyping and Gene Panel Sequencing Approaches Su...supporting
confidence: 68%
“…1 ). Previous studies have reported that mutations in 57 genes may cause or be associated with HCM, including eight definitive genes (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, ACTC1, MYL2 and MYL3), three moderately evidenced genes [cysteine and glycine-rich protein 3 (CSRP3), troponin C and junctophilin-2] and other genes with limited or no evidence (titin, Krueppel-like factor 10, myopalladin, ankyrin repeat domain-containing protein 1, myosin light chain kinase 2, myozenin-2, nexilin, vinculin, E3 ubiquitin-protein ligase TRIM63, ryanodine receptor 2, MYH6, obscurin, PDZ and LIM domain protein 3, telethonin, myomesin-1 and calreticulin-3) ( 23-27 ). Therefore, the present study focused on the genetic variations (SNPs and indels) occurring in any of the aforementioned genes.…”
Section: Resultsmentioning
confidence: 99%
“…Oligogenic inheritance of multiple pathogenic variants has been shown to cause CHDs 37 , 38 and cardiomyopathies. 39 While such studies showed multiple pathogenic variants can contribute to disease, our study showed pathogenic and protective variants in combination can provide the stable heritable transmission of an otherwise lethal mutation. It is worth noting that a study of genetic modifiers impacting ASD penetrance in heterozygous Nkx2.5 KO mice indicated p13q in a heterogeneous population, and the predominant modifiers are likely to be suppressors buffering against the pathogenic mutations.…”
Section: Discussionmentioning
confidence: 60%