Evidence map›Paper›PMID 40887606›Full record

ArticleOphthalmic genetics2025

Trio exome sequencing of an optic nerve hypoplasia cohort reveals evidence for polygenic architecture.

Jennifer G Aparicio, Kevin Stachelek, Pamela Garcia-Filion, Brianne Brown, Carly Stewart, David W Craig, Wenhui Laura Li, David Cobrinik, Mark Borchert

Abstract read
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In one paragraph

Article in Ophthalmic genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jennifer G AparicioThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-6442-3032
Kevin StachelekThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Pamela Garcia-FilionThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Brianne BrownThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Carly StewartThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
David W CraigDepartment of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Wenhui Laura LiDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA.
David CobrinikThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Mark BorchertThe Vision Center and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.

Funding

Modeling Optic Nerve Hypoplasia with Patient iPSC-Derived Retinal Ganglion CellsR21EY025419 · NEI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI BORCHERT, MARK STEPHEN, COBRINIK, DAVID · 2015 to 2016
$454k
NEI NIH HHS R21 EY025419
6 · The paper itself

Abstract

backgroundOptic nerve hypoplasia (ONH), the leading congenital cause of permanent blindness, is characterized by a retinal ganglion cell (RGC) deficit at birth and frequently associated neurologic and endocrine abnormalities. Multifactorial developmental events are hypothesized to underlie ONH; however, environmental influences are unclear, and genetic causes are under-investigated.

methodsTo identify monogenic, disease-causing variants among ONH patients, exomes from 34 ONH subjects and their parents were sequenced and rare variants identified. Inheritance-modelled variants were evaluated using population frequency, pathogenicity predictions, and mutational constraint metrics. Variants with the strongest genetic effect lacked evidence that they are monogenic and causal. All rare variants were filtered using mutational constraint metrics and pathogenicity predictions. The resultant variant-harboring genes were examined for recurrence within the cohort, gene ontology over-representation, RGC expression, and coincidence with neuro developmental disorder (NDD), autism, and previously proposed ONH genes.

resultsMutationally constrained genes with potentially pathogenic mutations were enriched in gene ontologies related to neuro developmental processes, were expressed in RGCs at significantly higher levels than random exome variant genes, and were enriched in autism and NDD-associated genes. Including the genes with strong genetic effect variants, these analyses call attention to 161 genes with potentially pathogenic variants that may contribute polygenic risk for ONH.

Indexed as

ExomeExome SequencingMultifactorial InheritanceMutationOptic Nerve HypoplasiaChildChild, PreschoolCohort StudiesFemaleHumansMaleRetinal Ganglion Cellscongenital blindnessOptic nerve hypoplasiaretinal ganglion cells

Identifiers

PMID40887606
PMCPMC12962389

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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.