Usually the report will indicate if the variant is pathogenic, variant of uncertain significance (VUS), or benign. autosomal dominant POLG and POLG2 pathogenic variants tend to have early onset and more severe mitochondrial presentations including myopathies. POLG and POLG2 are nuclear genes for mitochondrial DNA polymerase so deficits can result in accumulation of mitochondrial DNA mutations.
Best,
Drew
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Andrew Carey
Associate Professor
Wilmer Eye Institute, Johns Hopkins Medicine
Baltimore MD
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Original Message:
Sent: 11-04-2025 12:48
From: Eric Berman
Subject: POLG2 gene and optic atrophy
Greetings all,
I have a 20 year old male with bilateral optic atrophy. 20/20 vision in both eyes with essentially normal VF - referred for "glaucoma" evaluation. He has minimal complaints. Bilateral disc pallor and loss of NFL on OCT: 45/47 on Circumpapillary scan and 59/60 on ganglion cell OCT. I do not have any old records to say that any of this is new.
I ordered Genedx 615 panel – only thing that came back positive was POLg2 gene autosomal dominant variant c.590 T>C p.(L197P) – heterozygous.
Has anyone seen this particular variant in optic atrophy patient? Is this significant or is it not related? I am inclined to just follow him given his lack of complaints.
Thanks for your help.
ELB
Eric L. Berman, MD
Dr. William A. and Sandra F. Johnson Endowed Chair in Neuro-Ophthalmology
Director, Neuro-Ophthalmology Service
Storm Eye Institute
Medical University of South Carolina