Leber's Hereditary Optic Neuropathy, Intellectual Disability and Epilepsy Presenting with Variable Penetrance Associated to the M.3460G >A Mutation and a Heteroplasmic Expansion of the Microsatellite in MTRNR1 Gene - Case Report

Overview

Journal BMC Med Genet

Publisher Biomed Central

Specialty Genetics

Date 2018 Jul 29

PMID 30053855

Citations 5

Authors

Angelica Bianco

Luigi Bisceglia

Maria Fara De Caro

Valeria Galeandro

Patrizia De Bonis

Apollonia Tullo

Stefano Zoccolella

Silvana Guerriero

Vittoria Petruzzella

Affiliations

Soon will be listed here.

Abstract

Background: Leber's hereditary optic neuropathy (LHON) associated with mutations in mitochondrial DNA (mtDNA) typically manifests only optic nerve involvement but in some patients may develop additional neurological complications. The cause of this association is not clear.

Case Presentation: We present a case of a 24-year-old male with a history of subacute, painless, and rapidly progressive bilateral vision loss. We performed ophthalmological, neurological and neuropsychological investigations in the proband and his LHON family. The proband showed optic neuropathy, epilepsy, migraine, and intellectual disability; all the maternal relatives did not manifest optic neuropathy but a moderate to severe intellectual disability. Genetic screening revealed a novel association of the LHON m.3460G > A primary mutation with the m.T961delT + C(n)ins within the mitochondrial encoded 12S RNA (MTRNR1) gene which segregates with the intellectual disability through the maternal branch of the family. We also found a significant increase of mtDNA content in all the unaffected homo/heteroplasmic mutation carriers with respect to either affected or control subjects.

Conclusion: This is the first case reporting the co-segregation of a mutation in MTRNR1 gene with a LHON primary mutation, which may be a risk factor of the extraocular signs complicating LHON phenotype. In addition, the data herein reported, confirmed that the key factor modulating the penetrance of optic atrophy in the family is the amount of mtDNA.

Citing Articles

Mitochondrial translation defects and human disease.

Webb B, Diaz G, Prasun P J Transl Genet Genom. 2021; 4:71-80.

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CMT2A Harboring Mitofusin 2 Mutation with Optic Nerve Atrophy and Normal Visual Acuity.

Guerriero S, DOria F, Rossetti G, Favale R, Zoccolella S, Alessio G Int Med Case Rep J. 2020; 13:41-45.

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Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: Challenges and opportunities.

Bahr T, Welburn K, Donnelly J, Bai Y Biochim Biophys Acta Mol Basis Dis. 2020; 1866(6):165743.

PMID: 32105823 PMC: 9252426. DOI: 10.1016/j.bbadis.2020.165743.

Brain white matter changes in asymptomatic carriers of Leber's hereditary optic neuropathy.

Long M, Wang L, Tian Q, Ding H, Qin W, Shi D J Neurol. 2019; 266(6):1474-1480.

PMID: 30911824 DOI: 10.1007/s00415-019-09284-2.

Mitochondrial DNA copy number in affected and unaffected LHON mutation carriers.

Bianco A, Valletti A, Longo G, Bisceglia L, Montoya J, Emperador S BMC Res Notes. 2018; 11(1):911.

PMID: 30572950 PMC: 6302380. DOI: 10.1186/s13104-018-4025-y.

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