ArticleAmerican journal of human genetics2015
Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability.
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 45 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.Communications biology · 2023Pooled it
- Expanding the phenotypic spectrum associated with ZIC1 variants: A neurodevelopmental disorder with and without craniosynostosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Multi-omics integration reveals pan-cancer roles of ZIC family genes in prognosis, immune microenvironment remodeling, and therapeutic vulnerability.Discover oncology · 2026Article
- Unilateral craniosynostosis associated with ZIC1 gene mutation: a case report.Journal of surgical case reports · 2026Article
- Human cranial stem cells: developmental, pathologic, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Genetic Testing in Craniofacial Care: Development of Algorithms for Testing Patients with Orofacial Clefting, Branchial Arch Anomalies, and Craniosynostosis.The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association · 2025Article
- Non-syndromic craniosynostosis.Nature reviews. Disease primers · 2025Review
- Whole exome sequencing identifies ABHD14A and MRNIP as novel candidate genes for developmental language disorder.Scientific reports · 2025Article
- ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.Nature genetics · 2025Article
- TheFrontiers in medicine · 2025Review
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- Odd-Paired is Involved in Morphological Divergence of Snail-Feeding Beetles.Molecular biology and evolution · 2024Article
- Nanopore long-read sequencing analysis reveals ZIC1 dysregulation caused by a de novo 3q inversion with a breakpoint located 7 kb downstream of ZIC1.Journal of human genetics · 2024Article
- Regulatory elements inGenetics in medicine open · 2024Article
- Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.Nature communications · 2023Review
- ZIC1 Dictates Osteogenesis Versus Adipogenesis in Human Mesenchymal Progenitor Cells Via a Hedgehog Dependent Mechanism.Stem cells (Dayton, Ohio) · 2023Article
- Article
- Differential gene expression in the calvarial and cortical bone of juvenile female mice.Frontiers in endocrinology · 2023Article
- Never-homozygous genetic variants in healthy populations are potential recessive disease candidates.NPJ genomic medicine · 2022Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Human ZIC1 (zinc finger protein of cerebellum 1), one of five homologs of the Drosophila pair-rule gene odd-paired, encodes a transcription factor previously implicated in vertebrate brain development. Heterozygous deletions of ZIC1 and its nearby paralog ZIC4 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum, and loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects. We describe individuals from five families with heterozygous mutations located in the final (third) exon of ZIC1 (encoding four nonsense and one missense change) who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture. We conclude that the human mutations uncover a previously unsuspected role for Zic1 in early cranial suture development, potentially by regulating engrailed 1, which was previously shown to be critical for positioning of the murine coronal suture. The diagnosis of a ZIC1 mutation has significant implications for prognosis and we recommend genetic testing when common causes of coronal synostosis have been excluded.
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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.