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

Angelica Bianco, Luigi Bisceglia, Maria Fara De Caro, Valeria Galeandro, Patrizia De Bonis, Apollonia Tullo, Stefano Zoccolella, Silvana Guerriero, Vittoria Petruzzella

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number129
JournalBMC Medical Genetics
Volume19
Issue number1
DOIs
Publication statusPublished - Jul 27 2018

Keywords

  • Intellectual disability
  • LHON
  • M.3460G>A
  • Mitochondrial DNA
  • MTRNR
  • Penetrance

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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