ArticlePLoS genetics2022
Exome sequencing in multiplex families with left-sided cardiac defects has high yield for disease gene discovery.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01192048 (Genetic Testing of Individuals and Families With Congenital Heart Disease), which is not on this map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic Testing of Individuals and Families With Congenital Heart Disease
Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Synonymous variants in IRX4 and their association with congenital heart disease: an in-silico functional assessment.Molecular biology reports · 2026Article
- A machine learning classifier to identify and prioritise genes associated with murine cardiac development.PLoS genetics · 2026Article
- Protective role of Tongxinluo in mitigating myocardial fibrosis in mice with acute myocardial infarction via neuregulin-1 upregulation and Inhibition of endothelium-interstitial transition.Journal of molecular histology · 2025Article
- Hsf1 is essential for proteotoxic stress response in smyd1b-deficient embryos and fish survival under heat shock.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Heart Morphogenesis Requires Smyd1b for Proper Incorporation of the Second Heart Field in Zebrafish.Genes · 2025Article
- Four novel genetic mutations are associated with patent foramen ovale in Tibetan population using whole exome sequencing.Frontiers in genetics · 2025Article
- SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3β/β-catenin&ERK signaling.Stem cell research & therapy · 2024Article
- Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease.European journal of human genetics : EJHG · 2024Article
- Expression of Smyd1b_tv1 by Alternative Splicing in Cardiac Muscle is Critical for Sarcomere Organization in Cardiomyocytes and Heart Function.Molecular and cellular biology · 2024Article
- Novel pathogenic GATA6 variant associated with congenital heart disease, diabetes mellitus and necrotizing enterocolitis.Pediatric research · 2024Article
- Cardiomyocyte intercellular signalling increases oxidative stress and reprograms the global- and phospho-proteome of cardiac fibroblasts.Journal of extracellular biology · 2023Article
- CRISPR-based knockout and base editing confirm the role of MYRF in heart development and congenital heart disease.Disease models & mechanisms · 2023Article
- Review
- Identification of Two Homozygous Variants inGenes · 2023Article
- Graded mesoderm assembly governs cell fate and morphogenesis of the early mammalian heart.Cell · 2023Article
- Considering the Genetic Architecture of Hypoplastic Left Heart Syndrome.Journal of cardiovascular development and disease · 2022Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Congenital heart disease (CHD) is a common group of birth defects with a strong genetic contribution to their etiology, but historically the diagnostic yield from exome studies of isolated CHD has been low. Pleiotropy, variable expressivity, and the difficulty of accurately phenotyping newborns contribute to this problem. We hypothesized that performing exome sequencing on selected individuals in families with multiple members affected by left-sided CHD, then filtering variants by population frequency, in silico predictive algorithms, and phenotypic annotations from publicly available databases would increase this yield and generate a list of candidate disease-causing variants that would show a high validation rate. In eight of the nineteen families in our study (42%), we established a well-known gene/phenotype link for a candidate variant or performed confirmation of a candidate variant's effect on protein function, including variants in genes not previously described or firmly established as disease genes in the body of CHD literature: BMP10, CASZ1, ROCK1 and SMYD1. Two plausible variants in different genes were found to segregate in the same family in two instances suggesting oligogenic inheritance. These results highlight the need for functional validation and demonstrate that in the era of next-generation sequencing, multiplex families with isolated CHD can still bring high yield to the discovery of novel disease genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.