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A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance
  1. K P Burdon1,2,3,
  2. M G Wirth4,
  3. D A Mackey5,
  4. I M Russell-Eggitt6,
  5. J E Craig7,
  6. J E Elder5,
  7. J L Dickinson1,
  8. M M Sale1,2,8
  1. 1Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia
  2. 2Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
  3. 3Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  4. 4Department of Ophthalmology, University of Zürich, Zürich, Switzerland
  5. 5Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia
  6. 6Great Ormond St Hospital for Children, London, UK
  7. 7Department of Ophthalmology, Flinders University, Bedford Park, Australia
  8. 8Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  1. Correspondence to:
 Dr M M Sale
 Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA;

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Congenital or paediatric cataract is a phenotypically and genetically heterogeneous disorder consisting of lens opacities in early life. Thirteen genes have been described for autosomal dominant congenital cataract (ADCC). These include genes for seven members of the crystallin family,1,2 which are responsible for the refractive index and transparency of the lens, two connexin genes3,4 and major intrinsic protein of the lens (MIP)5 which are involved in the transport directly between cells of small metabolites and water, respectively, the cytoskeletal protein beaded filament structural protein-2 (BFSP2),6 and transcription factors paired-like homeodomain transcription factor-3 (PITX3)7 and heat shock factor-4 (HSF4).8 Five additional loci have been described on chromosomes 1pter-p36.1,9 15q21-q22,10 17p13,11 17q24,12 and 20p12-q12.13

We used a linkage approach to investigate these 13 genes and five loci in a large pedigree from Victoria, Australia, with zonular pulverulent cataract with the aim of identifying the causative mutation.


Ethics approval for this study was obtained from the Human Research Ethics Committees of the Royal Children’s Hospital, Melbourne, Australia, the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and the University of Tasmania, Hobart, Australia.

Patient ascertainment and collection of genetic material

The pedigree crch13 was identified through a database maintained by the Royal Children’s Hospital, Melbourne, Australia and the Royal Victorian Eye and Ear Hospital, Melbourne, comprising paediatric cataract patients from south-eastern Australia with any type of lens opacity.14 Written informed consent was obtained from all participating individuals or their guardians. When possible, family members were examined by one or more ophthalmologists (MGW, DAM, JEE, JEC, or IR-E). Due to the rural location of most family members, affection status was determined from medical records when direct examination was not feasible. In many cases pre-operative visual acuity was not available. Buccal mucosal swabs were either collected during examination …

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  • Grant support for this project was received from the Ophthalmic Research Institute of Australia, the Jack Brockhoff Foundation, and the Royal Hobart Hospital Research Foundation.

  • Conflict of interest: none declared.

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