ArticleAmerican journal of human genetics2000
Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.
Article in American journal of human genetics, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 293 citations in OpenAlex.
- Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.Human genetics · 2017Pooled it
- Deletions and loss-of-function variants in TP63 associated with orofacial clefting.European journal of human genetics : EJHG · 2019Trial
- Unveiling the Prevalence and Surgical Burden of Neurocristopathies: A Scoping Review and Statistical Analysis.Research square · 2026Article
- Malformation Pattern and Molecular Findings in theMedical sciences (Basel, Switzerland) · 2025Review
- Cleft Hand and Foot Syndrome: A Report of Three Cases with Review of Literature.Journal of orthopaedic case reports · 2025Article
- Article
- A novel approach to detecting microduplication in split hand/foot malformation type 3 at the single-cell level: SHFM as a case study.Orphanet journal of rare diseases · 2024Article
- Heterozygous TP63 pathogenic variants in isolated primary ovarian insufficiency.Journal of assisted reproduction and genetics · 2023Article
- A novel de novo TP63 mutation in whole-exome sequencing of a Syrian family with Oral cleft and ectrodactyly.Molecular genetics & genomic medicine · 2023Article
- A complex structural variant nearHGG advances · 2023Article
- A Rare Case Report of Split Hand and Foot Malformation.Journal of orthopaedic case reports · 2023Article
- A complex rearrangement betweenFrontiers in oncology · 2023Article
- Review
- Identification of a novel heterozygous missense TP63 variant in a Chinese pedigree with split-hand/foot malformation.BMC medical genomics · 2022Article
- Distinct interactors define the p63 transcriptional signature in epithelial development or cancer.The Biochemical journal · 2022Article
- Prenatal diagnosis of ectrodactyly-ectodermal dysplasia clefting syndrome ‒ a case report with literature review.Case reports in perinatal medicine · 2022Article
- Case report: Prenatal diagnosis of Ectrodactyly-Ectodermal dysplasia-Cleft syndrome (EEC) in a fetus with cleft lip and polycystic kidney.Frontiers in genetics · 2022Article
- Novel HOXD13 variants in syndactyly type 1b and type 1c, and a new spectrum of TP63-related disorders.Journal of human genetics · 2022Article
- Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools.Biomolecules · 2021Article
- Homozygous nonsense mutation ofThe Pan African medical journal · 2021Article
33 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
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Split-hand/split-foot malformation (SHFM), a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals, is phenotypically analogous to the naturally occurring murine Dactylaplasia mutant (Dac). Results of recent studies have shown that, in heterozygous Dac embryos, the central segment of the apical ectodermal ridge (AER) degenerates, leaving the anterior and posterior segments intact; this finding suggests that localized failure of ridge maintenance activity is the fundamental developmental defect in Dac and, by inference, in SHFM. Results of gene-targeting studies have demonstrated that p63, a homologue of the cell-cycle regulator TP53, plays a critically important role in regulation of the formation and differentiation of the AER. Two missense mutations, 724A-->G, which predicts amino acid substitution K194E, and 982T-->C, which predicts amino acid substitution R280C, were identified in exons 5 and 7, respectively, of the p63 gene in two families with SHFM. Two additional mutations (279R-->H and 304R-->Q) were identified in families with EEC (ectrodactyly, ectodermal dysplasia, and facial cleft) syndrome. All four mutations are found in exons that fall within the DNA-binding domain of p63. The two amino acids mutated in the families with SHFM appear to be primarily involved in maintenance of the overall structure of the domain, in contrast to the p63 mutations responsible for EEC syndrome, which reside in amino acid residues that directly interact with the DNA.
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.