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neurogenetics

, Volume 16, Issue 1, pp 69–75 | Cite as

Clinical and molecular genetic findings in autosomal dominant OPA3-related optic neuropathy

  • Panagiotis I. Sergouniotis
  • Rahat Perveen
  • Dawn L. Thiselton
  • Konstantinos Giannopoulos
  • Marios Sarros
  • Jennifer R. Davies
  • Susmito Biswas
  • Alec M. Ansons
  • Jane L. Ashworth
  • I. Christopher Lloyd
  • Graeme C. BlackEmail author
  • Marcela Votruba
Short Communication

Abstract

Leber hereditary optic neuropathy and autosomal dominant optic atrophy are the two most common inherited optic neuropathies. The latter has been associated with mutations in the OPA1 and OPA3 genes. To date, only six families with OPA3-associated dominant optic atrophy have been reported. In order to identify additional families, we performed Sanger sequencing of the OPA3 gene in 75 unrelated optic neuropathy patients. Affected individuals from two families were found to harbour the c.313C > G, p.(Gln105Glu) change in heterozygous state; this genetic defect has been previously reported in four dominant optic atrophy families. Intra- and interfamilial variability in age of onset and presenting symptoms was observed. Although dominant OPA3 mutations are typically associated with optic atrophy and cataracts, the former can be observed in isolation; we report a case with no lens opacities at age 38. Conversely, it is important to consider OPA3-related disease in individuals with bilateral infantile-onset cataracts and to assess optic nerve health in those whose vision fail to improve following lens surgery. The papillomacular bundle is primarily affected and vision is typically worse than 20/40. Notably, we describe one subject who retained normal acuities into the fifth decade of life. The condition can be associated with extraocular clinical features: two affected individuals in the present study had sensorineural hearing loss. The clinical heterogeneity observed in the individuals reported here (all having the same genetic defect in OPA3) suggests that the molecular pathology of the disorder is likely to be complex.

Keywords

OPA3 Optic atrophy Inherited optic neuropathy 3-methylglutaconic aciduria type III Congenital cataract Genetic ophthalmology 

Notes

Acknowledgments

Supported by the Medical Research Council UK (Grant G0500790), the Manchester Biomedical Research Centre and NIHR Greater Manchester: Clinical Research Network.

Supplementary material

10048_2014_416_MOESM1_ESM.doc (46 kb)
ESM 1 (DOC 46 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Panagiotis I. Sergouniotis
    • 1
    • 2
  • Rahat Perveen
    • 1
  • Dawn L. Thiselton
    • 3
    • 4
  • Konstantinos Giannopoulos
    • 4
  • Marios Sarros
    • 4
  • Jennifer R. Davies
    • 4
  • Susmito Biswas
    • 1
    • 2
  • Alec M. Ansons
    • 2
  • Jane L. Ashworth
    • 1
    • 2
  • I. Christopher Lloyd
    • 1
    • 2
  • Graeme C. Black
    • 1
    • 5
    • 7
    Email author
  • Marcela Votruba
    • 4
    • 6
  1. 1.Institute of Human Development, Faculty of Medical and Human SciencesUniversity of ManchesterManchesterUK
  2. 2.Manchester Royal Eye HospitalCentral Manchester University Hospitals NHS Foundation TrustManchesterUK
  3. 3.Virginia Institute of Psychiatric and Behavioural GeneticsVirginia Commonwealth UniversityRichmondUSA
  4. 4.School of Optometry and Vision SciencesCardiff UniversityCardiffUK
  5. 5.St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation TrustManchester Academic Health Science CentreManchesterUK
  6. 6.Cardiff Eye UnitUniversity Hospital WalesCardiffUK
  7. 7.St. Mary’s HospitalManchesterUK

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