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VSX2 in microphthalmia: a novel splice site mutation producing a severe microphthalmia phenotype
  1. Emma M M Burkitt Wright1,2,
  2. Rahat Perveen1,2,
  3. Naomi Bowers3,
  4. Simon Ramsden3,
  5. Emma McCann4,
  6. Mary O'Driscoll1,2,
  7. I Chris Lloyd1,5,
  8. Jill Clayton-Smith1,2,
  9. Graeme C M Black1,2
  1. 1Medical Genetics Research Group, University of Manchester and Central Manchester Hospitals Foundation Trust, St Mary's Hospital, Manchester, UK
  2. 2Department of Genetic and Developmental Medicine, Manchester Biomedical Research Centre, Central Manchester Hospitals Foundation Trust, Manchester, UK
  3. 3Manchester Regional Molecular Genetics Laboratory, Central Manchester Hospitals Foundation Trust, St Mary's Hospital, Manchester, UK
  4. 4North Wales Clinical Genetics Service, Rhyl, Denbighshire, UK
  5. 5Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, UK
  1. Correspondence to Professor Graeme C M Black, Medical Genetics Research Group, Genetic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9W2, UK; graeme.black{at}manchester.ac.uk

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Microphthalmia shows great genetic and clinical heterogeneity, whether as part of a syndrome or an isolated ocular phenotype. Chromosomal or single-gene disorders and teratogens may all cause microphthalmia. Associated syndromic features include cardiac problems, clefting, microcephaly and learning disabilities.1 Microphthalmia is frequently bilateral, but commonly asymmetrical in severity.

Homozygous mutations in VSX2/CHX10 have been demonstrated in human and murine microphthalmia.2 3 VSX2 is thought to act principally as a repressor of transcription, particularly of the genes encoding cyclin-dependent kinase inhibitor (p27kip1) and microphthalmia transcription factor (MITF).4 These repressive roles enable cell proliferation by preventing retinal progenitor cells from exiting the cell cycle, and by maintaining neuroretinal cell identity. Loss of these functions therefore causes failures in eye development. Other genes implicated in microphthalmia include SOX2, PAX6, sonic hedgehog (SHH), RAX, OTX2, CRYBA …

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