Research

Introduction
SOX2
Further Studies
Development Stages in Human Embryos

INTRODUCTION May 2003 (An article written by Nicola Ragge Moorfields)
Identifying Genes that cause Microphthalmia, Anophthalmia & Coloboma
Normal development of the eye is an extremely complex process that relies on a precisely arranged sequence of developmental steps. These steps are governed by control genes that are switched on and off at particular times of development. Most of the important development of eye structures in a developing baby is programmed to take place in the first 3 months of pregnancy. However, after this there are still some refinements that occur. Failure of any of the early eye development stages may cause anophthalmia (absent eye) and/or microphthalmia (small eye). Later events in pregnancy such as infections or exposure to chemicals may also cause microphthalmia, but usually not anophthalmia. In most cases the cause of these problems is not known.
SOX2 Gene
Recently through a collaboration of research between the MRC Human Genetics Unit in Edinburgh (Dr David Fitzpatrick and Professor Veronica van Heyningen) working together with Miss Nicola Ragge and Mr Richard Collin at Moorfields Eye Hospital identified an important gene, SOX2 which was shown to be mutated in about 10% of individuals with anophthalmia or microphthalmia (severe). This gene is known to be involved both in the out-pouching of the early brain to form the eyes and the formation of the lens. In everyone there are usually two active copies of this gene. It seems that if you only have one of the two normal copies of SOX2 this will cause anophthalmia. When we looked at the DNA of children with anophthalmia/microphthalmia we found that about 10% of them have a tiny genetic change on one copy of SOX2 which makes this copy inactive. In all the cases we have studied so far this change has occurred in the children for the first time and is not found in the parents. All these children had severe problems in both eyes. Changes in SOX2 do not seem to cause mild or unilateral microphthalmia or coloboma.

Further Studies

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We have only explained a very small proportion of cases so far and we are studying several other chromosomal mix-ups to see if we can identify other genes that may explain why these distressing birth defects occur. Nicola Ragge and Richard Collin run a specialist microphthalmia-anophthalmia clinic at Moorfields Eye Hospital where you or your child can receive overall supervision of socket growth, prosthetics (artificial eye), as well as input from a number of different clinical services including paediatrics, electro diagnostics (to determine how much vision is present), ultrasound (to determine the size and internal structures of the eyes), refraction (for glasses) and family support. We try to co-ordinate this so that as much as possible is achieved in a single visit, important if you need to travel a long distance. We also run a very large genetic study from this clinic. If you are interested in attending this clinic please ask your GP or local ophthalmologist to refer you there. If you are just interested in participating in the study, or for any further questions about the clinic please contact Miss Nicola Ragge, Adnexal Surgeon, Moorfields Eye Hospital, City Road, London EC1V 2PD. e-mail address: nragge@macs.org.uk

Development Stages in Human Embryos	Top

This article has very kindly been adapted for our website and would like to thank Dr David Fitzpatrick for his help in compiling the article. He can be contacted by e-mail at the following address Dr. David Fitzpatrick Senior Clinical Scientist MRC Human Genetics Unit Western General Hospital EDINBURGH EH4 2XU Email: david.fitzpatrick@hgu.mrc.ac.uk