Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2023 Mar 8:30:101825.
doi: 10.1016/j.ajoc.2023.101825. eCollection 2023 Jun.

Identification of AFG3L2 dominant optic atrophy following reanalysis of clinical exome sequencing

Michael C Brodsky  1   2 , Rory J Olson  3 , Faizal Z Asumda  4   5 , Madeline Q R Lopour  4 , Lisa A Schimmenti  4   6   7 , Eric W Klee  3
Affiliations
Case Reports

Identification of AFG3L2 dominant optic atrophy following reanalysis of clinical exome sequencing

Michael C Brodsky et al. Am J Ophthalmol Case Rep. .

Abstract

Purpose: To highlight the importance of the utility of clinical exome sequencing, and show how it led to the diagnosis of nonsyndromic autosomal dominant optic atrophy arising from an autosomal dominant variant in AFG3L2.

Observations: A healthy father and daughter of East African heritage experienced the onset of vision loss in the first decade of life due to optic atrophy. No additional neurologic or neuroimaging abnormalities were detected. Clinical exome sequencing was initially performed and provided a negative result. Reanalysis of the sequencing data revealed an autosomal dominant pathogenic variant in AFG3L2, c.1064C>T (p.Thr355Met), a gene that was recently identified to be associated with non-syndromic optic atrophy. This variant has previously been reported in a patient with optic atrophy, motor disturbances, and an abnormal brain MRI.

Conclusions: As the causes of dominant optic atrophy continue to expand, accurate genetic diagnosis is aided by an iterative reanalysis process for individuals and families when initial exome and genome testing does not provide an answer.

Keywords: AFG3L2 mutation; Dominant optic atrophy; SCA28.

PubMed Disclaimer

Conflict of interest statement

None. Supported in part by a grant from the 10.13039/100001209Knights Templar Eye Foundation, Flower Mound, TX (Dr Brodsky). The supporter had no input for the conduct of research and preparation of the article, study design, collection, analysis or collection of data, writing the report, and the decision to submit article for publication. All authors attest that they meet the current ICMJE criteria for authorship.

Figures

Fig. 1
Fig. 1
Optic disc photos in proband (case 1) showing small optic discs with wedge-shaped temporal pallor in both eyes. The nasal optic discs are less severely affected.
Fig. 2
Fig. 2
Optic disc photos in father (case 2) showing small optic discs with diffuse pallor, worse temporally, in both eyes.
See this image and copyright information in PMC

References

    1. Brodsky M.C. Springer; NY: 2016. Pediatric Neuro-Ophthalmology; pp. 222–227.
    1. Kjer P. Hereditary infantile optic atrophy with dominant transmission (preliminary report) Dan Med Bull. 1956;3:135–141. - PubMed
    1. Kline L.B., Glaser J.S. Dominant optic atrophy: the clinical profile. Arch Ophthalmol. 1979;97:1680–1686. - PubMed
    1. Hoyt C.S. Autosomal dominant optic atrophy. A spectrum of disability. Ophthalmology. 1980;87:245. - PubMed
    1. Eliott D., Traboulsi E.I., Maumenee I.H. Visual prognosis in autosomal dominant optic atrophy. Am J Ophthalmol. 1993;115:360–367. - PubMed

Publication types