Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene

Jason H. Peragallo, Stephanie Keller, Marjo S. van der Knaap, Bruno P. Soares, Suma P. Shankar

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.Materials and Methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.
Original languageEnglish
Pages (from-to)99-102
JournalOphthalmic Genetics
Volume39
Issue number1
DOIs
Publication statusPublished - 2018

Cite this

Peragallo, Jason H. ; Keller, Stephanie ; van der Knaap, Marjo S. ; Soares, Bruno P. ; Shankar, Suma P. / Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene. In: Ophthalmic Genetics. 2018 ; Vol. 39, No. 1. pp. 99-102.
@article{a00a453219a34ed8b29b1fbbe977aaf4,
title = "Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene",
abstract = "Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.Materials and Methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.",
author = "Peragallo, {Jason H.} and Stephanie Keller and {van der Knaap}, {Marjo S.} and Soares, {Bruno P.} and Shankar, {Suma P.}",
year = "2018",
doi = "10.1080/13816810.2017.1350723",
language = "English",
volume = "39",
pages = "99--102",
journal = "Ophthalmic Genetics",
issn = "1381-6810",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene. / Peragallo, Jason H.; Keller, Stephanie; van der Knaap, Marjo S.; Soares, Bruno P.; Shankar, Suma P.

In: Ophthalmic Genetics, Vol. 39, No. 1, 2018, p. 99-102.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene

AU - Peragallo, Jason H.

AU - Keller, Stephanie

AU - van der Knaap, Marjo S.

AU - Soares, Bruno P.

AU - Shankar, Suma P.

PY - 2018

Y1 - 2018

N2 - Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.Materials and Methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.

AB - Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.Materials and Methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027892773&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/28820624

U2 - 10.1080/13816810.2017.1350723

DO - 10.1080/13816810.2017.1350723

M3 - Article

VL - 39

SP - 99

EP - 102

JO - Ophthalmic Genetics

JF - Ophthalmic Genetics

SN - 1381-6810

IS - 1

ER -