The Double Mutation DSG2-p.S363X and TBX20-p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report

Myasnikov, R. P.; Brodehl, Andreas; Мешков, А. Н.; Куликова, О. В.; Киселева, А. В.; Pohl, Greta Marie; Sotnikova, Evgeniia A.; Divashuk, Mikhail G.; Климушина, М. В.; Zharikova, Anastasia A.; Pokrovskaya, M. S.; Koretsky, S. N.; Kharlap, M. S.; Мершина, Е. А.; Sinitsyn, V. E.; Басаргина, Е. Н.; Gandaeva, Leila; Barskiy, Vladimir; Boytsov, S. А.; Драпкина, О. М.

doi:10.3390/ijms22136775

Cited by 9 publications

(8 citation statements)

References 39 publications

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“…Molecular genetic investigation was carried out at the National Medical Research Center for Therapy and Preventive Medicine as we previously detailed in [ 12 ]. The investigated family members (i.e., patients II-2, III-1, III-2 and IV-1, see Figure 1 ) were subject to whole exome sequencing.…”

Section: Methodsmentioning

confidence: 99%

A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the FHOD3 Gene

Myasnikov

Букаева

Куликова

et al. 2022

Genes

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Left ventricular noncompaction (LVNC) is a highly heterogeneous primary disorder of the myocardium. Its clinical features and genetic spectrum strongly overlap with other types of primary cardiomyopathies, in particular, hypertrophic cardiomyopathy. Study and the accumulation of genotype–phenotype correlations are the way to improve the precision of our diagnostics. We present a familial case of LVNC with arrhythmic and thrombotic complications, myocardial fibrosis and heart failure, cosegregating with the splicing variant in the FHOD3 gene. This is the first description of FHOD3-dependent LVNC to our knowledge. We also revise the assumed mechanism of pathogenesis in the case of FHOD3 splicing alterations.

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Section: Methodsmentioning

confidence: 99%

A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the FHOD3 Gene

Myasnikov

Букаева

Куликова

et al. 2022

Genes

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“…23,28 Biallelic DSG2 pathogenic variants were associated with left ventricular noncompaction cardiomyopathy. 29 Case 5 with SUD had one likely pathogenic nonsense variant in the SCN5A gene and 2 missense VUS variants, one in the CASQ1 gene and the other in the SNTA1 gene. The SCN5A gene encodes an integral membrane protein and a tetrodotoxin-resistant voltage-gated sodium channel subunit.…”

Section: Discussionmentioning

confidence: 99%

“…In the literature, heterozygous DSG2 pathogenic variants have been associated with arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, and SUD 23,28 . Biallelic DSG2 pathogenic variants were associated with left ventricular noncompaction cardiomyopathy 29 …”

Section: Discussionmentioning

confidence: 99%

From Death to Life/Back to the Future: Detailed Premorbid Clinical and Family History Can Save Lives and Address the Final Diagnosis in Sudden Unexplained Deaths With Negative Autopsy

Turkgenc,

Baydar,

Deniz

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Sudden cardiac death is a sudden, unexpected death developed by one of the many different causes of cardiac arrest that occur within 1 hour of the onset of new symptoms. Sudden unexplained death (SUD) comprises a normal heart at postmortem examination and negative toxicological analysis. SUD often arises from cardiac genetic disease, particularly channelopathies. Channelopathies, or inherited arrhythmia syndromes, are a group of disorders characterized by an increased risk of sudden cardiac death, abnormal cardiac electrical function, and, typically, a structurally normal heart. They share an underlying genetic etiology where disease-causing genetic variants may lead to the absence or dysfunction of proteins involved in the generation and propagation of the cardiac action potential. Our study aimed to evaluate the importance of next-generation sequencing in the postmortem investigations of SUD cases. In this study, 5 forensic SUD cases were investigated for inherited cardiac disorders. We screened a total of 68 cardiac genes for the sibling of case 1, as well as case 2, and 51 genes for cases 3, 4, and 5. Of the 12 variants identified, 2 likely pathogenic variants (16.7%) were the TMEM43_ c.1000+2T>C splice site mutation and the SCN5A_ p.W703X nonsense mutation. The remaining 10 variants of uncertain significance were detected in the TRPM4, RANGRF, AKAP9, KCND3, KCNE1, DSG2, CASQ1, and SNTA1 genes. Irrespective of genetic testing, all SUD families require detailed clinical testing to identify relatives who may be at risk. Molecular autopsy and detailed premorbid clinical and family histories can survive family members of SUD cases.

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“…For the NextSeq 550 platform, exome libraries were prepared with the TruSeq DNA Library Preparation Kit (Illumina, San Diego, CA, USA) and the xGen Exome Research Panel (IDT, Integrated DNA Technologies, Coralville, IA, USA) according to the IDT-Illumina TruSeq DNA Exome protocol (Illumina, San Diego, CA, USA). Sequencing was done using NextSeq 550 (Illumina, San Diego, CA, USA) with paired-end sequencing (150 bp) ( 11 , 12 ).…”

Section: Methodsmentioning

confidence: 99%

Genetic landscape in Russian patients with familial left ventricular noncompaction

Мешков

Myasnikov

Киселева

et al. 2023

Front. Cardiovasc. Med.

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BackgroundLeft ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).MethodsAll index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.ResultsA total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants −8 of 54 (14.8%) −have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 −7.37; p <0.001) per variant after adjustment for sex, age, and family.ConclusionOverall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.

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The Double Mutation DSG2-p.S363X and TBX20-p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report

Cited by 9 publications

References 39 publications

A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the FHOD3 Gene

A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the FHOD3 Gene

From Death to Life/Back to the Future: Detailed Premorbid Clinical and Family History Can Save Lives and Address the Final Diagnosis in Sudden Unexplained Deaths With Negative Autopsy

Genetic landscape in Russian patients with familial left ventricular noncompaction

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