ArticleAmerican journal of human genetics2015
De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome.
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 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.Clinical endocrinology · 2026Pooled it
- Genome-wide association studies identify genetic determinants of synucleinopathy biomarkers.Research square · 2026Article
- Genome-wide association studies identify genetic determinants of synucleinopathy biomarkers.medRxiv : the preprint server for health sciences · 2025Article
- 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
- 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
- Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases.American journal of human genetics · 2024Article
- Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches.Scientific reports · 2023Article
- 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
- The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome.European journal of human genetics : EJHG · 2023Review
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
- De novo MCM6 variants in neurodevelopmental disorders: a recognizable phenotype related to zinc binding residues.Human genetics · 2023Article
- CDT1 is the major functional regulatory subunit of the pre-replication complex in zygotes.Cell proliferation · 2023Article
- Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation.Human molecular genetics · 2022Article
- Meier-Gorlin Syndrome: Clinical Misdiagnosis, Genetic Testing and Functional Analysis ofInternational journal of molecular sciences · 2022Article
- Intrinsic neural stem cell properties define brain hypersensitivity to genotoxic stress.Stem cell reports · 2022Article
- Article
- Homozygous mutation inJournal of medical genetics · 2022Article
- Time is of the essence: the molecular mechanisms of primary microcephaly.Genes & development · 2021Review
Corrections and comments
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Authors and funding
30 authors at 7 institutions in 2 countries.
Funding
Abstract
Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS.
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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.