Progressive optic nerve changes in cavitary optic disc anomaly: integration of copy number alteration and cis-expression quantitative trait loci to assess disease etiology

Eileen S Hwang; Denise J Morgan; Katie L Pennington; Leah A Owen; John H Fingert; Paul S Bernstein; Margaret M DeAngelis

doi:10.1186/s12881-019-0800-4

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Progressive optic nerve changes in cavitary optic disc anomaly: integration of copy number alteration and cis-expression quantitative trait loci to assess disease etiology

Journal article

Open access

Peer reviewed

Progressive optic nerve changes in cavitary optic disc anomaly: integration of copy number alteration and cis-expression quantitative trait loci to assess disease etiology

Eileen S Hwang, Denise J Morgan, Katie L Pennington, Leah A Owen, John H Fingert, Paul S Bernstein and Margaret M DeAngelis

BMC medical genetics, Vol.20(1), pp.63-63

04/27/2019

DOI: 10.1186/s12881-019-0800-4

PMCID: PMC6487068

PMID: 31029096

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Abstract

We performed clinical and genetic characterization of a family with cavitary optic disc anomaly (CODA), an autosomal dominant condition that causes vision loss due to adult-onset maculopathy in the majority of cases. CODA is characterized by a variably excavated optic nerve appearance such as morning glory, optic pit, atypical coloboma, and severe optic nerve cupping. Four affected and fourteen unaffected family members of a multi-generation pedigree were phenotyped by visual acuity, intraocular pressure, dilated fundus examination, fundus photography, and optical coherence tomography. Genetic analysis was performed by breakpoint polymerase chain reaction (PCR), long range PCR, and direct Sanger sequencing. The functional relevance of the copy number alteration region was assessed by in silico analysis. We found progressive optic nerve cupping in three affected members of a family with CODA. In one individual, an optic pit developed over time from a normal optic nerve. By two independent methods, we detected a previously described intergenic triplication that segregated with disease in all adults of the family. The copy number alteration was also detected in five children with normal optic nerves. eQTL analysis demonstrated that this CNA region regulates expression of up to 4 genes in cis. Morning glory, optic pit and atypical coloboma are currently considered congenital anomalies of the optic nerve, but our data indicate that in CODA, the excavated optic nerve appearance may develop after birth and into adulthood. In silico analysis of the CNA, may explain why vairable expressivity is observed in CODA.

Adolescent

Child

Child, Preschool

Disease Progression

DNA Copy Number Variations

Eye Abnormalities - etiology

Eye Abnormalities - genetics

Female

Humans

Male

Optic Disk - pathology

Optic Nerve - pathology

Pedigree

Quantitative Trait Loci

Details

Title: Subtitle: Progressive optic nerve changes in cavitary optic disc anomaly: integration of copy number alteration and cis-expression quantitative trait loci to assess disease etiology
Creators: Eileen S Hwang - University of Utah
Denise J Morgan - University of Utah
Katie L Pennington - University of Utah
Leah A Owen - University of Utah
John H Fingert - University of Iowa
Paul S Bernstein - University of Utah
Margaret M DeAngelis - University of Utah
Resource Type: Journal article
Publication Details: BMC medical genetics, Vol.20(1), pp.63-63
DOI: 10.1186/s12881-019-0800-4
PMID: 31029096
PMCID: PMC6487068
NLM abbreviation: BMC Med Genet
ISSN: 1471-2350
eISSN: 1471-2350
Grant note: P30 EY014800 / NEI NIH HHS T32 EY024234 / NEI NIH HHS
Language: English
Date published: 04/27/2019
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9984180932502771

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