ArticleHuman mutation2020
TBX6 missense variants expand the mutational spectrum in a non-Mendelian inheritance disease.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Genetics of non-isolated hemivertebra: A systematic review of fetal, neonatal, and infant cases.Clinical genetics · 2022Pooled it
- Article
- Review
- Deciphering the etiology of congenital scoliosis: A genetic and epigenetic perspective.World journal of orthopedics · 2025Review
- Preliminary study assessing the long-term surgical outcomes of TBX6-associated congenital scoliosis (TACS) patients using the propensity score matching method: exploring the clinical implications of genetic discoveries in congenital scoliosis.Orphanet journal of rare diseases · 2025Article
- Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis.Development (Cambridge, England) · 2024Article
- Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus.BMC pregnancy and childbirth · 2024Article
- Core planar cell polarity genesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine.Nature communications · 2024Article
- TBX6 as a cause of a combined skeletal-kidney dysplasia syndrome.American journal of medical genetics. Part A · 2022Article
- Developmental genomics of limb malformations: Allelic series in association with gene dosage effects contribute to the clinical variability.HGG advances · 2022Article
- Congenital scoliosis: a narrative review and proposal of a treatment algorithm.EFORT open reviews · 2022Review
- Delineation of dual molecular diagnosis in patients with skeletal deformity.Orphanet journal of rare diseases · 2022Article
- Molecular identification of T-box transcription factor 6 and prognostic assessment in patients with congenital scoliosis: A single-center study.Frontiers in medicine · 2022Article
- DisruptiveGenes · 2021Article
- Cross-sectional analysis and trend of vertebral and associated anomalies in Chinese congenital scoliosis population: a retrospective study of one thousand, two hundred and eighty nine surgical cases from 2010 to 2019.International orthopaedics · 2021Article
- Saturation mutagenesis defines novel mouse models of severe spine deformity.Disease models & mechanisms · 2021Article
- Variants Affecting the C-Terminal of CSF1R Cause Congenital Vertebral Malformation Through a Gain-of-Function Mechanism.Frontiers in cell and developmental biology · 2021Article
- Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS).Journal of medical genetics · 2021Article
- Mutational burden and potential oligogenic model of TBX6-mediated genes in congenital scoliosis.Molecular genetics & genomic medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors at 6 institutions in 2 countries.
Funding
Abstract
Congenital scoliosis (CS) is a birth defect with variable clinical and anatomical manifestations due to spinal malformation. The genetic etiology underlying about 10% of CS cases in the Chinese population is compound inheritance by which the gene dosage is reduced below that of haploinsufficiency. In this genetic model, the trait manifests as a result of the combined effect of a rare variant and common pathogenic variant allele at a locus. From exome sequencing (ES) data of 523 patients in Asia and two patients in Texas, we identified six TBX6 gene-disruptive variants from 11 unrelated CS patients via ES and in vitro functional testing. The in trans mild hypomorphic allele was identified in 10 of the 11 subjects; as anticipated these 10 shared a similar spinal deformity of hemivertebrae. The remaining case has a homozygous variant in TBX6 (c.418C>T) and presents a more severe spinal deformity phenotype. We found decreased transcriptional activity and abnormal cellular localization as the molecular mechanisms for TBX6 missense loss-of-function alleles. Expanding the mutational spectrum of TBX6 pathogenic alleles enabled an increased molecular diagnostic detection rate, provided further evidence for the gene dosage-dependent genetic model underlying CS, and refined clinical classification.
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.