A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction

Hirono, Keiichi; Hata, Yukiko; Ozawa, Sayaka; Toda, Takako; Momoi, Nobuo; Fukuda, Yutaka; Inuzuka, Ryo; Nagamine, Hiroki; Sakaguchi, Heima; Kurosaki, Kenichi; Okabe, Mako; Takarada, Shinya; Miyao, Nariaki; Nakaoka, Hideyuki; Ibuki, Keijiro; Origasa, Hideki; Bowles, Neil E.; Nishida, Naoki; Ichida, Fukiko

doi:10.1016/j.ijcard.2020.12.013

Cited by 6 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, many variants associated with human LVNC are sarcomere genes, part of myofibrillar structures, and are associated with contractile function, and alter the resulting protein rather than eliminate its function. Indeed, we reported that sarcomere variants are most commonly identified in fetus-onset patients, and fetus-onset patients with LVNC are more likely to develop HF (90). Moreover, we found a time-dependent increase in the ratio of noncompacted to compressible layers (N/C) of the LV wall in patients with fetal-onset LVNC, with the N/C ratio being greater than 2 before and after birth (91).…”

Section: Theoretical Gap Among Human and Non-human Models Or Congenit...mentioning

confidence: 73%

“…The prognosis of newborns with mitochondrial disease or metabolic complications is worse, with a higher rate of heart transplantation compared to DCM in children (17). Additionally, fetal-onset cases have a high rate of HF and mortality (5,90,91). In contrast, young and adult-onset cases that are asymptomatic and detected by medical examination or incidentally often have isolated LVNC, are asymptomatic for a long time, and have a good prognosis (17).…”

Section: Natural Historymentioning

confidence: 99%

See 1 more Smart Citation

Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity—a narrative review

Hirono¹,

Ichida²

2022

Cardiovasc Diagn Ther

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Theoretical Gap Among Human and Non-human Models Or Congenit...mentioning

confidence: 73%

Section: Natural Historymentioning

confidence: 99%

Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity—a narrative review

Hirono¹,

Ichida²

2022

Cardiovasc Diagn Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Seven cases had a pathological MYH7 mutation and, interestingly, other recent publications have demonstrated MYH7 mutations in fetuses with non‐compaction and hypertrophic CM 15–17 . Advanced genetic testing frequently detected variants of unknown significance, and we relied on genetic expertise to determine whether these were likely to be causative or represented incidental findings.…”

Section: Discussionmentioning

confidence: 99%

Clinical presentation, genetic etiology and outcome associated with fetal cardiomyopathy: comparison of two eras

Trakmulkichkarn

Ghadiry-Tavi

Fruitman

et al. 2022

Ultrasound in Obstet & Gyne

View full text Add to dashboard Cite

In the recent era, during which there has been improved access to genetic testing options, a higher proportion of fetal cardiomyopathy (CM) cases had an identifiable genetic etiology than reported previously. Despite recent major advances in perinatal management strategies, the postnatal outcome of this group of patients remains very poor. What are the clinical implications of this work?There is a critical role for genetic assessment and investigation of the family in cases of fetal CM. Interpretation of genetic test results is complex and the implications are multiple, including targeted screening of the extended family and recurrence-risk counseling in future pregnancies. Through provision of information on recent outcomes of a group of patients with fetal CM, the findings of this study should facilitate accurate counseling of families following a prenatal diagnosis of this rare condition.

show abstract

“…In one case (P6), this led to peacemaker implantation, while in the second case (P7) the disease course was complicated by HF. Recently, MYH7 pathogenic variants and VUSs have also been frequently identified in foetal-onset LVNC [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Profile of Left Ventricular Noncompaction Cardiomyopathy in Children—A Single Reference Center Experience

Piekutowska‐Abramczuk

Paszkowska

Ciara

et al. 2022

Genes

View full text Add to dashboard Cite

Background: Left ventricular noncompaction cardiomyopathy (LVNC) is a rare cardiac disorder characterised by the presence of a two-layer myocardium with prominent ventricular trabeculation, intertrabecular deep depressions and an increased risk of heart failure, atrial and ventricular arrhythmias and systemic thromboembolic events in affected patients. The heterogeneous molecular aetiology solved in 10%–50% of patients more frequently involves sarcomeric, cytoskeletal or ion channel protein dysfunction—mainly related to causative MYH7, TTN or MYBPC3 variants. The aim of the study was to determine the molecular spectrum of isolated LVNC in a group of children examined in a single paediatric reference centre. Methods: Thirty-one paediatric patients prospectively diagnosed with LVNC by echocardiography and cardiovascular magnetic resonance examination were recruited into the study group. The molecular analysis included next-generation sequencing (gene panel or whole exome) and classic Sanger sequencing. All selected variants with high priority were co-segregated in the available parents. Results: We identified 16 distinct variants in 11 genes in 16 patients (52%), including 10 novel alterations. The most frequent defects in our cohort were found in the genes HCN4 (n = 4), MYH7 (n = 2) and PRDM16 (n = 2). Other likely disease-causing variants were detected in ACTC1, ACTN2, HCCS, LAMA4, MYH6, RBM20, TAFFAZIN and TTN. Patients with established molecular defects more often presented with arrhythmia, thromboembolic events and death, whereas the predominant symptoms in patients with no identified molecular defects were heart failure and the presence of late gadolinium enhancement. Conclusion: This study expands the genetic and clinical spectrum of childhood LVNC. Although the molecular aetiology of LVNC varies widely, the comprehensive testing of a wide panel of cardiomyopathy-related genes helped to identify underlying molecular defects in more than half of the children in the study group. The molecular spectrum in our cohort correlated with the occurrence of arrhythmia, death and a family history of cardiomyopathy. We confirmed that genetic testing is an integral part of the work-up and management LVNC in children.

show abstract

A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction

Cited by 6 publications

References 22 publications

Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity—a narrative review

Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity—a narrative review

Clinical presentation, genetic etiology and outcome associated with fetal cardiomyopathy: comparison of two eras

Genetic Profile of Left Ventricular Noncompaction Cardiomyopathy in Children—A Single Reference Center Experience

Contact Info

Product

Resources

About