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J Med Genet 41:e109 doi:10.1136/jmg.2004.020289
  • Online mutation report

Recurrent 17 bp duplication in PITX3 is primarily associated with posterior polar cataract (CPP4)

  1. V Berry1,*,
  2. Z Yang3,*,
  3. P K F Addison1,2,
  4. P J Francis2,
  5. A Ionides2,
  6. G Karan3,
  7. L Jiang3,
  8. W Lin3,
  9. J Hu4,
  10. R Yang4,
  11. A Moore1,2,
  12. K Zhang3,
  13. S S Bhattacharya1
  1. 1Department of Molecular Genetics, Institute of Ophthalmology, University College of London, London, UK
  2. 2Moorfields Eye Hospital, London, UK
  3. 3Department of Ophthalmology and Visual Science, Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT, USA
  4. 4Chinese Academy of Military Science, Beijing, China
  1. Correspondence to:
 Dr V Berry
 Department of Molecular Genetics, Institute of Ophthalmology, London EC1V 9EL, UK; vberryhgmp.mrc.ac.uk
 Dr K Zhang
 Department of Ophthalmology and Visual Science, Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT, USA; kang.zhanghmbg.utah.edu
  • Received 4 April 2004
  • Accepted 6 April 2004

The human lens is a unique tissue continually evolving and ever increasing in size primarily formulated by placement of newly differentiated fibre cells in concentric lamellae. This is analogous to an onion skin arrangement. This differentiation triggers loss of both nucleus and other cell organelles. Furthermore, the main factors for maintaining lens clarity are the tight and ordered mutual binding of the fibre cells and the packing of their intracellular building blocks termed crystallins. It is known that lens transparency is a crucial trade-off between the concentration of these macromolecules and their hydration. Disruption of normal levels of hydration can lead to opacity.

Cataract, opacification of the eye lens, is the commonest cause of blindness in the world. During infancy and early childhood it frequently results in visual impairment or blindness. In children, it can cause an irreversible amblyopia. Nearly half of all congenital cataracts are normally characterised as familial and they are perceived to be a key feature if not the predominant feature of about 200 genetic diseases.1–3 Recent research has paved the way for a better understanding of the underlying mechanisms of inherited forms of cataract. Inherited cataract is clinically heterogeneous, and, thus far, more than 14 distinct loci in humans have been identified, for 11 phenotypically distinct forms of autosomal dominant congenital cataracts (ADCC).4,5

Progress has been made in elucidating cataract causing mutations in human genes encoding the transparent intracellular lens proteins (crystallins), membrane gap junction proteins (connexins), water channel proteins (aquaporins), developmental transcription factors FOXE3,6 EYA1,7PAX6,8MAF,9 and PITX3.10 Based on this insight, it can be deduced that cataracts exhibit marked phenotypic and genotypic heterogeneity.

Here we report a number of interesting findings about the PITX3 gene: (1) we have found mutations in …