ArticleAmerican journal of medical genetics. Part A2011
Variants in genes that encode muscle contractile proteins influence risk for isolated clubfoot.
Article in American journal of medical genetics. Part A, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Unraveling the Genetic Landscape of Foot Arch Morphology: A Systematic Review of Single Nucleotide Polymorphisms.Clinical genetics · 2025Pooled it
- The etiology of idiopathic congenital talipes equinovarus: a systematic review.Journal of orthopaedic surgery and research · 2018Pooled it
- Genetics, epidemiology and management of clubfoot and related disorders.Genes & diseases · 2025Review
- Association of Polymorphism in Locus of rs274503 (Genetic testing and molecular biomarkers · 2024Article
- Incidence and prevalence of congenital clubfoot in Apulia: a regional model for future prospective national studies.Italian journal of pediatrics · 2023Review
- Genetic Role in Recurrence of Idiopathic CTEV: A Systematic Review.Orthopedic research and reviews · 2023Review
- Diagnostic yield of exome sequencing in congenital vertical talus.European journal of medical genetics · 2022Article
- Clubfoot treatment in China before and after the advent of the Ponseti technique: a historical narrative review.Annals of translational medicine · 2021Review
- Integrated Bioinformatics Analysis Reveals Potential Pathway Biomarkers and Their Interactions for Clubfoot.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Association of single nucleotide polymorphisms in the 3'UTR region of TPM1 gene with dilated cardiomyopathy: A case-control study.Medicine · 2019Article
- The genetics of isolated and syndromic clubfoot.Journal of children's orthopaedics · 2019Article
- The developmental and genetic basis of 'clubfoot' in the peroneal muscular atrophy mutant mouse.Development (Cambridge, England) · 2018Article
- Functional Assessment of Clubfoot Associated HOXA9, TPM1, and TPM2 Variants Suggests a Potential Gene Regulation Mechanism.Clinical orthopaedics and related research · 2016Article
- A systematic review of association studies of common variants associated with idiopathic congenital talipes equinovarus (ICTEV) in humans in the past 30 years.SpringerPlus · 2016Review
- Heritability of clubfoot: a twin study.Journal of children's orthopaedics · 2014Article
- Identification of an FHL1 protein complex containing gamma-actin and non-muscle myosin IIB by analysis of protein-protein interactions.PloS one · 2013Article
- Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot.American journal of medical genetics. Part A · 2012Article
Corrections and comments
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Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
Abstract
Isolated clubfoot is a relatively common birth defect that affects approximately 4,000 newborns in the US each year. Calf muscles in the affected leg(s) are underdeveloped and remain small even after corrective treatment. This observation suggests that variants in genes that influence muscle development are priority candidate risk factors for clubfoot. This contention is further supported by the discovery that mutations in genes that encode components of the muscle contractile complex (MYH3, TPM2, TNNT3, TNNI2, and MYH8) cause congenital contractures, including clubfoot, in distal arthrogryposis (DA) syndromes. Interrogation of 15 genes encoding proteins that control myofiber contractility in a cohort of both non-Hispanic White (NHW) and Hispanic families, identified positive associations (P < 0.05) with SNPs in 12 genes; only 1 was identified in a family-based validation dataset. Six SNPs in TNNC2 deviated from Hardy-Weinberg equilibrium in mothers in our NHW discovery dataset. Relative risk and likelihood ratio tests showed evidence for a maternal genotypic effect with TNNC2/rs383112 and an inherited/child genotypic effect with two SNPs, TNNC2/rs4629 and rs383112. Associations with multiple SNPs in TPM1 were identified in the NHW discovery (rs4075583, P = 0.01), family-based validation (rs1972041, P = 0.000074), and case-control validation (rs12148828, P = 0.04) datasets. Gene interactions were identified between multiple muscle contraction genes with many of the interactions involving at least one potential regulatory SNP. Collectively, our results suggest that variation in genes that encode contractile proteins of skeletal myofibers may play a role in the etiology of clubfoot.
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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.