ArticleThe Journal of clinical investigation2012
Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.
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Who cites it
160 citing papers in PubMed, 1 synthesis or guideline pooled it, 301 citations in OpenAlex.
- Immunogenetics of gastrointestinal cancers: A systematic review and retrospective survey of inborn errors of immunity in humans.Journal of gastroenterology and hepatology · 2022Pooled it
- Trial
- Loss of minichromosome maintenance 4 leads to early renal dysplasia and cystogenesis outcomes.Genes & diseases · 2026Article
- MCM3 Safeguards Neural Progenitor Maintenance and Cortical Development Against Replication-Associated Stress.Molecular neurobiology · 2026Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- Autosomal dominant CDC45 deficiency with allelic expression bias causes a novel genetic disease of the immune system.bioRxiv : the preprint server for biology · 2026Article
- Multilocus pathogenic variants inAME case reports · 2026Article
- Inborn errors of immunity with DNA repair disorders: at the interface of immune deficiency, immune dysregulation, and malignancy.Frontiers in immunology · 2026Review
- Article
- Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.Cell reports · 2025Article
- Oncolytic adenovirus serotype 35 mediated tumor growth suppressionJournal for immunotherapy of cancer · 2025Article
- Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?Pathogens (Basel, Switzerland) · 2025Review
- Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients.The Journal of experimental medicine · 2025Article
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.Cell reports · 2025Article
- Site directed mutagenesis reveals functional importance of conserved amino acid residues within the N-terminal domain of Dpb2 in budding yeast.Archives of microbiology · 2024Article
- Tissue-specific features of innate lymphoid cells in antiviral defense.Cellular & molecular immunology · 2024Review
- Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Review
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
100 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
Natural killer (NK) cells are circulating cytotoxic lymphocytes that exert potent and nonredundant antiviral activity and antitumoral activity in the mouse; however, their function in host defense in humans remains unclear. Here, we investigated 6 related patients with autosomal recessive growth retardation, adrenal insufficiency, and a selective NK cell deficiency characterized by a lack of the CD56(dim) NK subset. Using linkage analysis and fine mapping, we identified the disease-causing gene, MCM4, which encodes a component of the MCM2-7 helicase complex required for DNA replication. A splice-site mutation in the patients produced a frameshift, but the mutation was hypomorphic due to the creation of two new translation initiation methionine codons downstream of the premature termination codon. The patients' fibroblasts exhibited genomic instability, which was rescued by expression of WT MCM4. These data indicate that the patients' growth retardation and adrenal insufficiency likely reflect the ubiquitous but heterogeneous impact of the MCM4 mutation in various tissues. In addition, the specific loss of the NK CD56(dim) subset in patients was associated with a lower rate of NK CD56(bright) cell proliferation, and the maturation of NK CD56(bright) cells toward an NK CD56(dim) phenotype was tightly dependent on MCM4-dependent cell division. Thus, partial MCM4 deficiency results in a genetic syndrome of growth retardation with adrenal insufficiency and selective NK deficiency.
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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.