Title |
Leber Hereditary Optic Neuropathy in a Family of Carriers of MT-ND5 m.13042G>T (A236S) Novel Variant |
Creator |
Sanja Petrović Pajić; Maja Suštar Habjan; Jelka Brecelj; Ana Fakin; Marija Volk; Aleš Maver; Gregor Jezernik; Borut Peterlin; Damjan Glavač; Marko Hawlina; Martina Jarc-Vidmar |
Affiliation |
Eye Hospital (SPP, MJV, BSK, MS, JB, AF, MSH), University Medical Centre Ljubljana, Ljubljana, Slovenia; Clinic for Eye Diseases (SPP), Clinical Centre of Serbia, Belgrade, Serbia; Department of Molecular Genetics (DG), Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Center for Human Genetics and Pharmacogenomics (GJ, DG), Faculty of Medicine, University of Maribor, Maribor, Slovenia; Clinical Institute of Genomic Medicine (MV, AM, BP), University Medical Centre Ljubljana, Ljubljana, Slovenia |
Abstract |
Background: A Slovenian three-generation family with 3 individuals with bilateral optic neuropathy and 2 unaffected relatives with a novel homoplasmic missense variant m.13042G > T (A236S) in the ND5 gene is described. A detailed phenotype at initial diagnosis and a follow-up of bilateral optic neuropathy progression is presented for 2 affected individuals. Methods: A detailed phenotype analysis with clinical examination in the early and chronic phase with electrophysiology and OCT segmentation is presented. Genotype analysis with full mitochondrial genome sequencing was performed. Results: Two affected male individuals (maternal cousins) had a profound visual loss at an early age (11 and 20 years) with no recovery. The maternal grandmother exhibited bilateral optic atrophy with a history of visual loss at the age 58 years. The visual loss of both affected male individuals was characterized by centrocecal scotoma, abnormal color vision, abnormal PERG N95, and VEP. Later with disease progression, retinal nerve fiber layer thinning was observed on OCT. We observed no other extraocular clinical features. Mitochondrial sequencing identified a homoplasmic novel variant m.13042G > T (A236S) in the MT-ND5 gene, belonging to a haplogroup K1a. Conclusions: Novel homoplasmic variant m.13042G > T (A236S) in the ND5 gene in our family was associated with Leber hereditary optic neuropathy-like phenotype. However, predicting the pathogenicity of a novel ultra-rare missense variant in the mitochondrial ND5 gene is challenging. Genetic counseling should consider genotypic and phenotypic heterogeneity, incomplete penetrance, haplogroup type, and tissue-specific thresholds. |
Subject |
Blindness; DNA, Mitochondrial / genetics; Humans; Male; Mitochondria / genetics; Mutation; Optic Atrophy, Hereditary, Leber / diagnosis; Optic Atrophy, Hereditary, Leber / genetics; Pedigree; Phenotype; Vision Disorders |
Date |
2023-09 |
Date Digital |
2023-09 |
Language |
eng |
Format |
application/pdf |
Type |
Text |
Publication Type |
Journal Article |
Source |
Journal of Neuro-Ophthalmology, September 2023, Volume 43, Issue 3 |
Collection |
Neuro-Ophthalmology Virtual Education Library: Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher |
Lippincott, Williams & Wilkins |
Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
Rights Management |
© North American Neuro-Ophthalmology Society |
ARK |
ark:/87278/s6673ktc |
Setname |
ehsl_novel_jno |
ID |
2538077 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6673ktc |