ArticleHuman molecular genetics2018
Dysregulation of TBX1 dosage in the anterior heart field results in congenital heart disease resembling the 22q11.2 duplication syndrome.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Reduced dosage of Kmt2d modifies Tbx1 haploinsufficiency toward phenotypes of 22q11.2DS.JCI insight · 2026Article
- Functional noncoding variants within the TBX1 enhancer contribute to tetralogy of Fallot.Science China. Life sciences · 2026Article
- Dark and camouflaged genomic regions remain challenging in CHM13.Scientific reports · 2026Article
- Sequencing the gaps: dark genomic regions persist in CHM13 despite long-read advances.bioRxiv : the preprint server for biology · 2025Article
- Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve.Heart (British Cardiac Society) · 2025Observational
- Tbx1 haploinsufficiency leads to local skull deformity, paraflocculus and flocculus dysplasia, and motor-learning deficit in 22q11.2 deletion syndrome.Nature communications · 2024Article
- Prenatal diagnosis in fetal right aortic arch using chromosomal microarray analysis and whole exome sequencing: a Chinese single-center retrospective study.Molecular cytogenetics · 2024Article
- The yield of SNP microarray analysis for fetal ultrasound cardiac abnormalities.BMC pregnancy and childbirth · 2024Article
- Molecular Pathways and Animal Models of Truncus Arteriosus.Advances in experimental medicine and biology · 2024Review
- A Multicenter Analysis of Abnormal Chromosomal Microarray Findings in Congenital Heart Disease.Journal of the American Heart Association · 2023Article
- Immunologic, Molecular, and Clinical Profile of Patients with Chromosome 22q11.2 Duplications.Journal of clinical immunology · 2023Article
- The frequency and efficacy of genetic testing in individuals with scimitar syndrome.Cardiology in the young · 2022Article
- Variants in a cis-regulatory element of TBX1 in conotruncal heart defect patients impair GATA6-mediated transactivation.Orphanet journal of rare diseases · 2021Article
- Mending a broken heart:Disease models & mechanisms · 2021Review
- New Concepts in the Development and Malformation of the Arterial Valves.Journal of cardiovascular development and disease · 2020Review
- Genetic Basis of Human Congenital Heart Disease.Cold Spring Harbor perspectives in biology · 2020Article
- The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life.Fetal diagnosis and therapy · 2020Review
- HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans.American journal of human genetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Non-allelic homologous recombination events on chromosome 22q11.2 during meiosis can result in either the deletion (22q11.2DS) or duplication (22q11.2DupS) syndrome. Although the spectrum and frequency of congenital heart disease (CHD) are known for 22q11.2DS, there is less known for 22q11.2DupS. We now evaluated cardiac phenotypes in 235 subjects with 22q11.2DupS including 102 subjects we collected and 133 subjects that were previously reported as a confirmation and found 25% have CHD, mostly affecting the cardiac outflow tract (OFT). Previous studies have shown that global loss or gain of function (LOF; GOF) of mouse Tbx1, encoding a T-box transcription factor mapping to the region of synteny to 22q11.2, results in similar OFT defects. To further evaluate Tbx1 function in the progenitor cells forming the cardiac OFT, termed the anterior heart field, Tbx1 was overexpressed using the Mef2c-AHF-Cre driver (Tbx1 GOF). Here we found that all resulting conditional GOF embryos had a persistent truncus arteriosus (PTA), similar to what was previously reported for conditional Tbx1 LOF mutant embryos. To understand the basis for the PTA in the conditional GOF embryos, we found that proliferation in the Mef2c-AHF-Cre lineage cells before migrating to the heart, was reduced and critical genes were oppositely changed in this tissue in Tbx1 GOF embryos versus conditional LOF embryos. These results suggest that a major function of TBX1 in the AHF is to maintain the normal balance of expression of key cardiac developmental genes required to form the aorta and pulmonary trunk, which is disrupted in 22q11.2DS and 22q11.2DupS.
Indexed as
Identifiers
What OpenQuestion holds
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.