Long-term screening for primary mitochondrial DNA variants associated with Leber hereditary optic neuropathy: incidence, penetrance and clinical features

Mitochondrion. 2020 Sep:54:128-132. doi: 10.1016/j.mito.2020.08.007. Epub 2020 Aug 28.


Leber hereditary optic neuropathy (LHON) is a neurodegenerative disorder characterised by bilateral, painless, subacute, central vision loss caused by pathogenic sequence variants in mitochondrial DNA (mtDNA). Over the course of 20 years, 734 people were systematically screened by our diagnostic laboratory for suspected LHON or for being at risk of LHON, with 98 found to harbour one of the three primary pathogenic mtDNA variants. Detection incidences were: 0.95% for NC_012920.1(MT-ND1):m.3460G>A; 9.4% for (MT-ND4):m.11778G>A; and 2.9% for (MT-ND6):m.14484T>C. The median age for symptomatic males was 27.3 years and for females 29.5 years, with a male to female ratio of 4.4:1 (62 males; 14 females). Most pathogenic variant carriers were propositi with the other individuals belonging to one of 14 pedigrees with noteworthy intra-family variability of clinical severity of the disease.

Keywords: Leber hereditary optic neuropathy (LHON); Maternal inheritance; Mitochondria; Optic atrophy; mtDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • DNA, Mitochondrial / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mutation Rate
  • NADH Dehydrogenase / genetics*
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Pedigree
  • Penetrance
  • Polymorphism, Single Nucleotide*


  • DNA, Mitochondrial
  • NADH dehydrogenase subunit 4
  • MT-ND6 protein, human
  • NADH Dehydrogenase
  • MT-ND1 protein, human