Genetic aetiology of ophthalmological manifestations in children - a focus on mitochondrial disease-related symptoms

Acta Ophthalmol. 2016 Feb;94(1):83-91. doi: 10.1111/aos.12897. Epub 2015 Oct 8.


Purpose: To investigate the association of mutations in the mitochondrial DNA (mtDNA) or nuclear candidate genes with mitochondrial disease-related ophthalmic manifestations (nystagmus, ptosis, ophthalmoplegia, optic neuropathy and retinopathy) in children.

Methods: A retrospective cohort of children (n = 98) was identified from the medical record files of a tertiary care hospital. The entire mtDNA and nuclear genes POLG1, OPA1 and PEO1 were analysed from the available DNA samples (n = 38). Furthermore, some nuclear candidate genes were investigated based on family history and phenotype. Rare mtDNA mutations were evaluated using in silico predictors and sequence alignment.

Results: Three patients had previously identified mutations in mtDNA that are associated with optic neuropathy (in MT-ND6 and MT-ND1) and nystagmus (in tRNA Arg). Nine rare mutations in MT-ATP6 were identified in seven patients, of whom four manifested with retinopathy and three had clusters of MT-ATP6 mutations. Nuclear PEO1 and OPA1 were unchanged in all samples, but a patient with nystagmus had a heterozygous POLG1 mutation. The analysis of nuclear candidate genes revealed mutations in NDUF8 (patient with nystagmus), TULP1 (patient with optic neuropathy, nystagmus and retinopathy) and RP2 (patient with retinopathy) genes.

Conclusions: Children with retinopathy, nystagmus or optic neuropathy, especially together with developmental delay or positive family history, should be considered for mitochondrial disease. MT-ATP6 should be taken into account for children with retinopathy of unknown aetiology.

Keywords: MT-ATP6; genetics; mitochondrial diseases; nystagmus; optic neuropathy; paediatrics; ptosis; retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blepharoptosis / genetics
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics*
  • DNA-Directed DNA Polymerase / genetics
  • Eye Diseases / genetics*
  • Female
  • Genome, Mitochondrial*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Mutation*
  • Nystagmus, Pathologic / genetics
  • Ophthalmoplegia / genetics
  • Optic Nerve Diseases / genetics
  • Retinal Diseases / genetics
  • Retrospective Studies


  • DNA, Mitochondrial
  • MT-ATP6 protein, human
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • Mitochondrial Proton-Translocating ATPases