ArticleThe Journal of clinical investigation2012
MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans.
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 132 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
132 citing papers in PubMed, 259 citations in OpenAlex.
- Autosomal dominant CDC45 deficiency with allelic expression bias causes a novel genetic disease of the immune system.bioRxiv : the preprint server for biology · 2026Article
- Identification of novel and recurrent mutations in nicotinamide nucleotide transhydrogenase (Journal of clinical & translational endocrinology · 2026Article
- Inborn errors of immunity with DNA repair disorders: at the interface of immune deficiency, immune dysregulation, and malignancy.Frontiers in immunology · 2026Review
- Multilocus pathogenic variants inAME case reports · 2026Article
- The impact of genetic immune disorders on infections including COVID-19, inflammatory bowel disease and cancer.Nature immunology · 2025Review
- Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.Cell reports · 2025Article
- Due-B Is dispensable for early development and genome duplication in vertebrates.bioRxiv : the preprint server for biology · 2025Article
- Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients.The Journal of experimental medicine · 2025Article
- Is the vIL-10 Protein from Cytomegalovirus Associated with the Potential Development of Acute Lymphoblastic Leukemia?Viruses · 2025Review
- 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
- Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Follow up of a rare case of adrenal insufficiency due toBMJ case reports · 2024Article
- Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications.Virology journal · 2024Review
- Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency.The Journal of allergy and clinical immunology · 2024Article
- A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells.Open biology · 2024Article
- Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines.Chemical reviews · 2023Review
- Comment on: "The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome" by Nielsen-Dandoroff et al.European journal of human genetics : EJHG · 2023Article
- An integrated single-cell analysis of human adrenal cortex development.JCI insight · 2023Article
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
An interesting variant of familial glucocorticoid deficiency (FGD), an autosomal recessive form of adrenal failure, exists in a genetically isolated Irish population. In addition to hypocortisolemia, affected children show signs of growth failure, increased chromosomal breakage, and NK cell deficiency. Targeted exome sequencing in 8 patients identified a variant (c.71-1insG) in minichromosome maintenance-deficient 4 (MCM4) that was predicted to result in a severely truncated protein (p.Pro24ArgfsX4). Western blotting of patient samples revealed that the major 96-kDa isoform present in unaffected human controls was absent, while the presence of the minor 85-kDa isoform was preserved. Interestingly, histological studies with Mcm4-depleted mice showed grossly abnormal adrenal morphology that was characterized by non-steroidogenic GATA4- and Gli1-positive cells within the steroidogenic cortex, which reduced the number of steroidogenic cells in the zona fasciculata of the adrenal cortex. Since MCM4 is one part of a MCM2-7 complex recently confirmed as the replicative helicase essential for normal DNA replication and genome stability in all eukaryotes, it is possible that our patients may have an increased risk of neoplastic change. In summary, we have identified what we believe to be the first human mutation in MCM4 and have shown that it is associated with adrenal insufficiency, short stature, and NK cell deficiency.
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.