ArticleThe Journal of clinical investigation2013
PRKDC mutations in a SCID patient with profound neurological abnormalities.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 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
87 citing papers in PubMed, 151 citations in OpenAlex.
- Base editing reversal of radiation sensitivity in NHEJ1 immunodeficiency.Journal of human immunity · 2026Article
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- Exercise alone or combined with functional foods in aging and age-related diseases: targeting DNA damage, repair pathways, and genome integrity.Frontiers in aging neuroscience · 2026Review
- Ku limits aberrant mRNA splicing promoted by intronic antisense Alu elements.bioRxiv : the preprint server for biology · 2025Article
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 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
- Compared to other NHEJ factors, DNA-PK protein and RNA levels are markedly increased in all higher primates, but not in prosimians or other mammals.DNA repair · 2024Article
- Cilia defects upon loss of WDR4 are linked to proteasomal hyperactivity and ubiquitin shortage.Cell death & disease · 2024Article
- The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.EMBO reports · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Multi-omics analysis of a case of congenital microtia reveals aldob and oxidative stress associated with microtia etiology.Orphanet journal of rare diseases · 2024Article
- Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex.Journal of inflammation (London, England) · 2024Article
- DNA damage response-related ncRNAs as regulators of therapy resistance in cancer.Frontiers in pharmacology · 2024Review
- DNA-PKcs and ATM modulate mitochondrial ADP-ATP exchange as an oxidative stress checkpoint mechanism.The EMBO journal · 2023Article
- Two distinct long-range synaptic complexes promote different aspects of end processing prior to repair of DNA breaks by non-homologous end joining.Molecular cell · 2023Article
- Kinome-wide screening uncovers a role for Bromodomain Protein 3 in DNA double-stranded break repair.DNA repair · 2023Article
- Targeting DNA-PK.Cancer treatment and research · 2023Article
- High Throughput Genetic Characterisation of Caucasian Patients Affected by Multi-Drug Resistant Rheumatoid or Psoriatic Arthritis.Journal of personalized medicine · 2022Article
- Inborn errors of immunity associated with defects of thymic development.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022Review
- Inborn errors of immunity caused by defects in the DNA damage response pathways: Importance of minimizing treatment-related genotoxicity.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022Review
27 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
11 authors at 7 institutions in 3 countries.
Funding
Abstract
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs; encoded by PRKDC) functions in DNA non-homologous end-joining (NHEJ), the major DNA double strand break (DSB) rejoining pathway. NHEJ also functions during lymphocyte development, joining V(D)J recombination intermediates during antigen receptor gene assembly. Here, we describe a patient with compound heterozygous mutations in PRKDC, low DNA-PKcs expression, barely detectable DNA-PK kinase activity, and impaired DSB repair. In a heterologous expression system, we found that one of the PRKDC mutations inactivated DNA-PKcs, while the other resulted in dramatically diminished but detectable residual function. The patient suffered SCID with reduced or absent T and B cells, as predicted from PRKDC-deficient animal models. Unexpectedly, the patient was also dysmorphic; showed severe growth failure, microcephaly, and seizures; and had profound, globally impaired neurological function. MRI scans revealed microcephaly-associated cortical and hippocampal dysplasia and progressive atrophy over 2 years of life. These neurological features were markedly more severe than those observed in patients with deficiencies in other NHEJ proteins. Although loss of DNA-PKcs in mice, dogs, and horses was previously shown not to impair neuronal development, our findings demonstrate a stringent requirement for DNA-PKcs during human neuronal development and suggest that high DNA-PK protein expression is required to sustain efficient pre- and postnatal neurogenesis.
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.