ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2016
Copy number variation as a genetic basis for heterotaxy and heterotaxy-spectrum congenital heart defects.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 44 citations in OpenAlex.
- Gpr101 expression during early stages of murine development.Gene expression patterns : GEP · 2025Article
- Genomic rare variant mechanisms for congenital cardiac laterality defect: A digenic model approach.American journal of human genetics · 2025Article
- Application of copy number variation sequencing combined with whole exome sequencing in prenatal left-right asymmetry disorders.BMC genomics · 2025Article
- Expanding the Molecular Spectrum ofGenes · 2025Review
- Optical genome mapping uncovers clinically relevant structural variants in congenital heart disease with heterotaxy.Frontiers in genetics · 2025Article
- The genetic landscape of cardiovascular left-right patterning defects.Current opinion in genetics & development · 2022Review
- Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study.Orphanet journal of rare diseases · 2022Article
- Understanding laterality disorders and the left-right organizer: Insights from zebrafish.Frontiers in cell and developmental biology · 2022Review
- Spectrum of Genetic Variants in a Cohort of 37 Laterality Defect Cases.Frontiers in genetics · 2022Article
- Genetic and Clinical Features of Heterotaxy in a Prenatal Cohort.Frontiers in genetics · 2022Article
- Article
- Loss of vacuolar-type H+-ATPase induces caspase-independent necrosis-like death of hair cells in zebrafish neuromasts.Disease models & mechanisms · 2021Article
- A novel heterotaxy gene: Expansion of the phenotype of TTC21B-spectrum disease.American journal of medical genetics. Part A · 2021Article
- Aquatic models of human ciliary diseases.Genesis (New York, N.Y. : 2000) · 2021Review
- Genetic Basis of Human Congenital Heart Disease.Cold Spring Harbor perspectives in biology · 2020Article
- The Role of Non-Coding RNA in Congenital Heart Diseases.Journal of cardiovascular development and disease · 2019Review
- Rare Copy Number Variations Might Not be Involved in the Molecular Pathogenesis of PA-IVS in an Unselected Chinese Cohort.Pediatric cardiology · 2019Article
- Genetic evaluation of patients with congenital heart disease.Current opinion in pediatrics · 2018Review
- Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association.Circulation · 2018Review
- Rare copy number variants analysis identifies novel candidate genes in heterotaxy syndrome patients with congenital heart defects.Genome medicine · 2018Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic disorders and rare copy number abnormalities are identified in 15-25% of patients with syndromic conditions, but their prevalence in individuals with isolated birth defects is less clear. A spectrum of congenital heart defects (CHDs) is seen in heterotaxy, a highly heritable and genetically heterogeneous multiple congenital anomaly syndrome resulting from failure to properly establish left-right (L-R) organ asymmetry during early embryonic development. To identify novel genetic causes of heterotaxy, we analysed copy number variants (CNVs) in 225 patients with heterotaxy and heterotaxy-spectrum CHDs using array-based genotyping methods. Clinically relevant CNVs were identified in approximately 20% of patients and encompassed both known and putative heterotaxy genes. Patients were carefully phenotyped, revealing a significant association of abdominal situs inversus with pathogenic or likely pathogenic CNVs, while d-transposition of the great arteries was more frequently associated with common CNVs. Identified cytogenetic abnormalities ranged from large unbalanced translocations to smaller, kilobase-scale CNVs, including a rare, single exon deletion in ZIC3, a gene known to cause X-linked heterotaxy. Morpholino loss-of-function experiments in Xenopus support a role for one of these novel candidates, the platelet isoform of phosphofructokinase-1 (PFKP) in heterotaxy. Collectively, our results confirm a high CNV yield for array-based testing in patients with heterotaxy, and support use of CNV analysis for identification of novel biological processes relevant to human laterality.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.
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