ArticleAmerican journal of human genetics2016
Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 118 citations in OpenAlex.
- 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
- Molecular diagnosis of rare biallelic CDC45 gene variants causing Meier-Gorlin syndrome-7 using whole exome sequencing.Human genomics · 2026Article
- Identification of a novel and a recurrentFrontiers in genetics · 2026Article
- Unexpected molecular mechanism of Orc6-based Meier-Gorlin syndrome: insights from a humanized Drosophila model.Genetics · 2025Article
- Anesthetic management in a child with Meier-Gorlin syndrome: a case report.BMC anesthesiology · 2025Article
- The genetic basis of human height.Nature reviews. Genetics · 2025Review
- Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.Cell reports · 2025Article
- Identification of MCM2-Interacting Proteins Associated with Replication Initiation Using APEX2-Based Proximity Labeling Technology.International journal of molecular sciences · 2025Article
- A novel homozygous intronic variant in CDT1 that alters splicing causes Meier-Gorlin syndrome, and a review of published mutations and growth hormone treatments.Orphanet journal of rare diseases · 2024Review
- 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
- Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.Molecular systems biology · 2024Article
- Comprehensive analysis ofTranslational andrology and urology · 2024Article
- A second hotspot for pathogenic exon-skipping variants in CDC45.European journal of human genetics : EJHG · 2024Article
- Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans.Genes · 2024Review
- The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome.European journal of human genetics : EJHG · 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
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
- Article
- Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation.Human molecular genetics · 2022Article
13 more citing papers are in PubMed but not listed here.
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34 authors at 16 institutions in 10 countries.
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Abstract
DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis.
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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.