ArticleEuropean journal of human genetics : EJHG2019
Genetic architecture of laterality defects revealed by whole exome sequencing.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Genetics in Heterotaxy: A Case Series and Literature Review on DNAH9, PKD1L1, MMP21, and GDF1.Clinical genetics · 2026Pooled it
- Engineered human induced pluripotent stem cell models reveal altered podocytogenesis in congenital heart disease-associated SMAD2 mutations.Nature biomedical engineering · 2026Article
- Molecular characterization of FAM222B as a novel disease gene for dominant cardiovascular laterality defects.Scientific reports · 2026Article
- Global research trends in heterotaxy syndrome with congenital heart defects: a 20-year bibliometric analysis (2006-2025).Translational pediatrics · 2026Article
- Further Support for Association ofGenes · 2026Article
- Article
- Laterality and Completeness Patterns of Nonsyndromic Clefts in a Multiethnic Cohort.medRxiv : the preprint server for health sciences · 2026Article
- The Ultrasound and Genetic Characteristics of Fetuses With Laterality Defects-A Prenatal Cohort in Asian Population.Prenatal diagnosis · 2025Article
- Genomic rare variant mechanisms for congenital cardiac laterality defect: A digenic model approach.American journal of human genetics · 2025Article
- Genetic impact of copy number variations on congenital heart defects: Current insights and future directions.Global medical genetics · 2025Review
- CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.American journal of human genetics · 2025Article
- Unmasking a Recessive Allele by a Rare Interstitial Deletion at 10q26.13q26.2: Prenatal Diagnosis of MMP21 -Related Disorder and Further Refine INSYN2A Involvement in the Postnatal Cognitive Phenotype.Molecular genetics & genomic medicine · 2025Article
- Expanding the Molecular Spectrum ofGenes · 2025Review
- Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population.Frontiers in genetics · 2025Article
- Rare homozygous cilia gene variants identified in consanguineous congenital heart disease patients.Human genetics · 2024Article
- Non-coding cause of congenital heart defects: Abnormal RNA splicing with multiple isoforms as a mechanism for heterotaxy.HGG advances · 2024Article
- Investigation of the genetic and clinical features of laterality disorders in prenatal diagnosis: discovery of a novel compound heterozygous mutation in the DNAH11 gene.Archives of gynecology and obstetrics · 2024Article
- Primary Ciliary Dyskinesia: A Clinical Review.Cells · 2024Review
- A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy.BMC neurology · 2024Article
- NODAL variants are associated with a continuum of laterality defects from simple D-transposition of the great arteries to heterotaxy.Genome medicine · 2024Article
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Authors and funding
31 authors at 5 institutions in 1 country.
Funding
Abstract
Aberrant left-right patterning in the developing human embryo can lead to a broad spectrum of congenital malformations. The causes of most laterality defects are not known, with variants in established genes accounting for <20% of cases. We sought to characterize the genetic spectrum of these conditions by performing whole-exome sequencing of 323 unrelated laterality cases. We investigated the role of rare, predicted-damaging variation in 1726 putative laterality candidate genes derived from model organisms, pathway analyses, and human phenotypes. We also evaluated the contribution of homo/hemizygous exon deletions and gene-based burden of rare variation. A total of 28 candidate variants (26 rare predicted-damaging variants and 2 hemizygous deletions) were identified, including variants in genes known to cause heterotaxy and primary ciliary dyskinesia (ACVR2B, NODAL, ZIC3, DNAI1, DNAH5, HYDIN, MMP21), and genes without a human phenotype association, but with prior evidence for a role in embryonic laterality or cardiac development. Sanger validation of the latter variants in probands and their parents revealed no de novo variants, but apparent transmitted heterozygous (ROCK2, ISL1, SMAD2), and hemizygous (RAI2, RIPPLY1) variant patterns. Collectively, these variants account for 7.1% of our study subjects. We also observe evidence for an excess burden of rare, predicted loss-of-function variation in PXDNL and BMS1- two genes relevant to the broader laterality phenotype. These findings highlight potential new genes in the development of laterality defects, and suggest extensive locus heterogeneity and complex genetic models in this class of birth defects.
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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.