Nuclear DNA Mutation Causing a Phenotypic Leber Hereditary Optic Neuropathy Plus

Mansukhani, Sasha A.; Mehta, Dev; Renaud, Deborah L.; Whealy, Mark A.; Chen, John J.; Bhatti, M. Tariq

doi:10.1016/j.ophtha.2020.09.011

Cited by 17 publications

(21 citation statements)

References 6 publications

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“…6 The remaining 10% of cases are the result of point mutations at other mtDNA positions as well as within the nuclear DNA. 7 The classic presentation of LHON is acute to subacute, painless, central visual loss that may progress over weeks to months. In up to 50% of cases the visual loss is bilateral and simultaneous, and in the other half it is sequential with second eye involvement usually within 3 months.…”

Section: Discussionmentioning

confidence: 99%

Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

2022

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A 31-year-old healthy white male experienced painless sequential vision loss. Brain imaging and laboratory investigations for infectious, inflammatory, and nutritional conditions, in addition to targeted genetic testing for Leber hereditary optic neuropathy (LHON), were all normal or negative. Despite systemic corticosteroid therapy and plasma exchange, vision continued to worsen. Eventually, mitochondrial whole genome sequencing was performed, which demonstrated a mutation at the 13513G>A position confirming the diagnosis of LHON. Three primary mutations (11778G>A, 14484T>C and 3460G>A) account for 90% of LHON cases, therefore it is important to consider whole genome mitochondrial sequencing in cases with a high index of clinical suspicion.

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Section: Discussionmentioning

confidence: 99%

Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

2022

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“…Brain imaging demonstrates consistent involvement of the basal ganglia (Bi et al, 2021;Gerards et al, 2010;Mansukhani et al, 2021;Simon et al, 2019). Seizures and delayed growth are common in the early onset form but unlikely in the later onset.…”

Section: Discussionmentioning

confidence: 99%

Case report of atypical Leigh syndrome in an adolescent male with novel biallelic variants in NDUFAF5 and review of the natural history of NDUFAF5‐related disorders

Legro

Kumar

Aliu

2021

American J of Med Genetics Pt A

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NDUFAF5 encodes a Complex I assembly factor which is critical to the modification of a core subunit, NDUFS7, in early Complex I factor assembly. Mutations in NDUFAF5 have been previously shown to cause Complex I deficiency leading to mitochondrial respiratory chain impairment. More than 15 individuals affected by variants in NDUFAF5 have been described; however, there is phenotypic heterogeneity within this cohort. Some individuals display features of classical Leigh syndrome with early onset neurodegeneration whereas others live into early adulthood with progressive neurological deficits. Here, we present a clinical report of a 17-year-old African American individual with compound heterozygous mutations in NDUFAF5.The individual presented with childhood onset bilateral optic atrophy and developed progressive neuromuscular decline with relatively preserved cognition over time.

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“…LHON has been recently associated with peculiar combinations of individually non‐pathogenic missense mtDNA variants, affecting genes for mtDNA‐encoded CI subunits 2 . Very interestingly, several genetic variants in nuclear DNA (nDNA) genes, such as NDUFS2 that codes for a CI structural subunit; NDUFAF5 that codes for a CI assembly factor; and DNAJC30 that codes for a chaperone protein needed for CI repair have been also associated with LHON 3,4 . Therefore, a dysfunctional CI appears to be the main etiologic factor for LHON.…”

Section: Introductionmentioning

confidence: 99%

“…NDUFAF5 that codes for a CI assembly factor; and DNAJC30 that codes for a chaperone protein needed for CI repair have been also associated with LHON. 3,4 Therefore, a dysfunctional CI appears to be the main etiologic factor for LHON.…”

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confidence: 99%

Toxic and nutritional factors trigger Leber hereditary optic neuropathy due to a mitochondrial tRNA mutation

et al. 2022

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Leber hereditary optic neuropathy is a mitochondrial disease mainly due to pathologic mutations in mitochondrial genes related to the respiratory complex I of the oxidative phosphorylation system. Genetic, physiological, and environmental factors modulate the penetrance of these mutations. We report two patients suffering from this disease and harboring a m.15950G > A mutation in the mitochondrial DNA-encoded gene for the threonine transfer RNA. We also provide evidences supporting the pathogenicity of this mutation.

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Nuclear DNA Mutation Causing a Phenotypic Leber Hereditary Optic Neuropathy Plus

Cited by 17 publications

References 6 publications

Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

Case report of atypical Leigh syndrome in an adolescent male with novel biallelic variants in NDUFAF5 and review of the natural history of NDUFAF5‐related disorders

Toxic and nutritional factors trigger Leber hereditary optic neuropathy due to a mitochondrial tRNA mutation

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