ArticleThe New England journal of medicine2015
TBX6 null variants and a common hypomorphic allele in congenital scoliosis.
Article in The New England journal of medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 4 of them syntheses 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
191 citing papers in PubMed, 4 syntheses or guidelines pooled it, 313 citations in OpenAlex.
- Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review.Journal of human genetics · 2024Pooled it
- Genetics of non-isolated hemivertebra: A systematic review of fetal, neonatal, and infant cases.Clinical genetics · 2022Pooled it
- Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits.Genome medicine · 2022Pooled it
- Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese.Nature communications · 2019Pooled it
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- Article
- Advances in the etiology of congenital scoliosis: from morphology to spatiotemporal molecular mechanisms (2015-2025).EFORT open reviews · 2026Article
- [Prenatal ultrasound and genetic characteristics of 60 fetuses with 16p11.2 microdeletion].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Article
- Runx2 mutation plays a key role in the development of scoliosis.Innovation (Cambridge (Mass.)) · 2026Review
- Admixture-driven structural variation diversity and its functional implications.National science review · 2026Article
- A hypomorphic SRD5A2 haplotype with a potential founder effect: composed of common variants in individuals with 5α-reductase type 2 deficiency from South China.Biology of sex differences · 2026Article
- Deciphering the Genetic Basis of Congenital Vertebral Malformations Through a Stepwise Diagnostic Approach.International journal of molecular sciences · 2026Article
- The role of genetics and molecular mechanisms in early onset scoliosis.Journal of clinical orthopaedics and trauma · 2026Review
- MicroRNA network regulation of developmental bone toxicity in a human embryonic stem cell osteogenic model.NAM journal · 2026Article
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- Whole-Exome Sequencing of Discordant Monozygotic Twins for Congenital Scoliosis: A Family Case Study.Genes · 2025Article
- Exploring genotype-phenotype correlation of a novel SHOX gene splicing variant: Langer mesomelic dysplasia or idiopathic short stature.Molecular biology reports · 2025Article
- Vitamin A Deficiency Induces Congenital Vertebral Malformation via Retinoic Acid Signaling Mediated Sclerotome Dysplasia.Neurospine · 2025Article
- Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects.BMC pregnancy and childbirth · 2025Article
131 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
58 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCongenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis.
methodsWe evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multicenter series of 42 persons with 16p11.2 deletions.
resultsWe identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10(-6)). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis.
conclusionsCompound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. (Funded by the National Basic Research Program of China and others.).
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.