ArticleHuman molecular genetics2012
ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Lineage Tracing Reveals atoh7-Positive and Negative Retinal Ganglion Cell Populations in the Zebrafish Retina.Investigative ophthalmology & visual science · 2026Article
- Genetic associations of variants in 10 glaucoma-related genes with POAG risk and structural phenotypes in Korean subjects.Medicine · 2026Article
- Lineage tracing revealsbioRxiv : the preprint server for biology · 2026Article
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- NovelInternational journal of ophthalmology · 2025Article
- Multi-dataset identification of innovative feature genes and molecular mechanisms in keratoconus.Journal of cellular and molecular medicine · 2024Article
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- A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis.Cell reports · 2024Article
- Pathogenetic Insights into Developmental Coordination Disorder Reveal Substantial Overlap with Movement Disorders.Brain sciences · 2023Article
- Single-Cell Characterization of the Frizzled 5 (Fz5) Mutant Mouse and Human Persistent Fetal Vasculature (PFV).Investigative ophthalmology & visual science · 2023Article
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- Persistent Hyperplastic Primary Vitreous with Microphthalmia and Coloboma in a Patient with Okur-Chung Neurodevelopmental Syndrome.Molecular syndromology · 2022Article
- Functional Characterization of an In-Frame Deletion in the Basic Domain of the Retinal Transcription Factor ATOH7.International journal of molecular sciences · 2022Article
- A single-cell guide to retinal development: Cell fate decisions of multipotent retinal progenitors in scRNA-seq.Developmental biology · 2021Review
- Mechanistic Insights into Axenfeld-Rieger Syndrome from ZebrafishInternational journal of molecular sciences · 2021Review
- Atoh7-independent specification of retinal ganglion cell identity.Science advances · 2021Article
- Identification of Key Genes and Pathways in Persistent Hyperplastic Primary Vitreous of the Eye Using Bioinformatic Analysis.Frontiers in medicine · 2021Article
- Outcomes and surgical management of persistent fetal vasculature.BMJ open ophthalmology · 2021Article
- Retinal ganglion cell interactions shape the developing mammalian visual system.Development (Cambridge, England) · 2020Review
- TheProceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
14 authors at 9 institutions in 4 countries.
Funding
Abstract
The vertebrate basic helix-loop-helix (bHLH) transcription factor ATOH7 (Math5) is specifically expressed in the embryonic neural retina and is required for the genesis of retinal ganglion cells (RGCs) and optic nerves. In Atoh7 mutant mice, the absence of trophic factors secreted by RGCs prevents the development of the intrinsic retinal vasculature and the regression of fetal blood vessels, causing persistent hyperplasia of the primary vitreous (PHPV). We therefore screened patients with hereditary PHPV, as well as bilateral optic nerve aplasia (ONA) or hypoplasia (ONH), for mutations in ATOH7. We identified a homozygous ATOH7 mutation (N46H) in a large family with an autosomal recessive PHPV disease trait linked to 10q21, and a heterozygous variant (R65G, p.Arg65Gly) in one of five sporadic ONA patients. High-density single-nucleotide polymorphism analysis also revealed a CNTN4 duplication and an OTX2 deletion in the ONA cohort. Functional analysis of ATOH7 bHLH domain substitutions, by electrophoretic mobility shift and luciferase cotransfection assays, revealed that the N46H variant cannot bind DNA or activate transcription, consistent with structural modeling. The N46H variant also failed to rescue RGC development in mouse Atoh7-/- retinal explants. The R65G variant retains all of these activities, similar to wild-type human ATOH7. Our results strongly suggest that autosomal recessive persistent hyperplastic primary vitreous is caused by N46H and is etiologically related to nonsyndromic congenital retinal nonattachment. The R65G allele, however, cannot explain the ONA phenotype. Our study firmly establishes ATOH7 as a retinal disease gene and provides a functional basis to analyze new coding variants.
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