ArticleAmerican journal of human genetics2015
Mutations in the NHEJ component XRCC4 cause primordial dwarfism.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 83 citations in OpenAlex.
- Machine learning insights into obesity related genes XRCC4 and ARL6 in obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung · 2025Article
- Characterization of a PNLIP variant identified in Amish pediatric patients with congenital pancreatic lipase deficiency.Journal of lipid research · 2025Article
- B-cell immunodeficiency associated with polynucleotide kinase 3'-phosphatase (PNKP) deficiency.The journal of allergy and clinical immunology. Global · 2025Article
- Epidemiological Surveillance of Genetically Determined Microcephaly in Latin America: A Narrative Review.Epidemiologia (Basel, Switzerland) · 2025Review
- XRCC4-related microcephalic primordial dwarfism: description of a clinical series of 7 cases, phenotype expansion and new diagnostic approaches.European journal of human genetics : EJHG · 2025Article
- LAP1 Interactome Profiling Provides New Insights into LAP1's Physiological Functions.International journal of molecular sciences · 2024Article
- Cilia defects upon loss of WDR4 are linked to proteasomal hyperactivity and ubiquitin shortage.Cell death & disease · 2024Article
- Quantitative proteome analysis of LAP1-deficient human fibroblasts: A pilot approach for predicting the signaling pathways deregulated in LAP1-associated diseases.Biochemistry and biophysics reports · 2024Article
- DNA Repair Enzyme XRCC4 30 bp Indel Intron 3 Locus Significant Association with Predisposition of Cataract in Senility.Applied biochemistry and biotechnology · 2024Article
- Article
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
- Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy.Nature communications · 2022Article
- Exploring the Origin and Physiological Significance of DNA Double Strand Breaks in the Developing Neuroretina.International journal of molecular sciences · 2022Review
- Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining.Nucleic acids research · 2022Article
- Feline XRCC4 undergoes rapid Ku-dependent recruitment to DNA damage sites.FEBS open bio · 2022Article
- NGS-Based B-Cell Receptor Repertoire AnalysisRepertoire analyses in the Context of Inborn Errors of Immunity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Association of Polymorphisms in NHEJ Pathway Genes with HIV-1 Infection and AIDS Progression in a Northern Chinese MSM Population.Disease markers · 2022Article
- Cornelia de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect.Nature communications · 2021Article
- Functional analysis of XRCC4 mutations in reported microcephaly and growth defect patients in terms of radiosensitivity.Journal of radiation research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 12 institutions in 8 countries.
Funding
Abstract
Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation.
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.