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Online mutation report
A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract
  1. C E Willoughby2,*,
  2. Sara Arab3,*,
  3. R Gandhi1,
  4. S Zeinali4,
  5. Seddigheh Arab4,
  6. D Luk1,
  7. G Billingsley1,
  8. F L Munier5,
  9. E Héon2
  1. 1Vision Science Research Program, Toronto Western Hospital, Toronto, Canada
  2. 2Department of Opthalmology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
  3. 3Department of Cardiology, Heart and Stroke, Richard Lewar Centre of Excellence, Toronto General Hospital, University of Toronto
  4. 4Pasteur Institute, Tehran, Islamic Republic of Iran
  5. 5Ocular Genetics Unit, Hôpital Jules Gonin, Lausanne, Switzerland
  1. Correspondence to:
 Dr E Héon
 Department of Ophthalmology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; eheonattglobalnet.com

https://doi.org/10.1136/jmg.40.11.e124

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    Cataract results from a loss in transparency of the crystalline lens. Worldwide, there are an estimated 20 million people blind (Snellen visual acuity of 3/60 or less) as a result of cataract.1 Despite effective surgical treatment, demand outstrips supply in both Western and developing countries, for many reasons,2,3 and other disease modifying strategies must be considered. A strong genetic predisposition to the development of congenital cataract and age related cataract has been well documented.4,5 Inherited cataract accounts for at least 50% of all congenital cataracts,6 and shows marked inter- and intrafamilial variation.7 Twin studies on age related cataracts in the United Kingdom estimate that two thirds of cortical cataract and at least half of nuclear cataracts can be explained by genetic factors.8,9

    Previous genetic studies of congenital cataracts identified connexin 50 (Cx50) as a cataract related gene.10–12 Here we report a novel heterozygous R23T mutation in the GJA8 gene (MIM#600897) encoding connexin 50, in an Iranian family affected by a progressive autosomal dominant congenital nuclear cataract. In addition, to determine the genetic contribution of connexin 50 mutations to the basis of congenital and age related cataracts for our mutation (R23T) and the other three published Cx50 mutations (P88S, E48K, and I247M)10–12, two additional patient populations were screened for those changes.

    Key points

    • The molecular characterisation of an Iranian family with an autosomal dominant progressive congenital nuclear cataract is described. Affected members were found to have a novel heterozygous missense mutation R23T in the GJA8 gene encoding connexin 50 (Cx50). This sequence change segregated with the disease phenotype in the family and was not found in 152 control individuals, including 52 ethnically matched controls.

    • This non-conservative mutation replaces an evolutionary conserved basic polar charged amino acid by …

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