EPOS

European Paediatric Ophthalmological Society

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35 Chromosomal rearrangements and lens and anterior segment development.

Jamieson, R.¹, Donnai, D.i¹, Kerr, B.¹, Carette, M.², Black, G.¹
University Department of Medical Genetics and Regional Genetic Service, St Mary's Hospital, Hathersage Rd, Manchester, UK, Department of Clinical Genetics, Royal Manchester Children's Hospital, Pendlebury, Manchester, UK.

Purpose: In the majority of cases of hereditary congenital cataract and anterior segment dysgenesis, the underlying genetic cause is unknown. We have identified families with chromosomal rearrangements (translocations and deletions) with cataract and anterior segment abnormality. Clinical ocular and genetic assessment has been used to determine those families where breakpoint identification would be likely to pinpoint novel genes in lens and anterior segment development. We are undertaking molecular analysis for candidate gene detection in these families.

Methods: The families with the chromosomal rearrangements were identified through referral to the genetic eye clinic. Individuals were clinically assessed and in selected cases, somatic cell hybrids were established. Molecular identification of the breakpoints is proceeding in these cases.

Results: Family 1: An individual and his father with a balanced translocation both have cataract. Offspring with an unbalanced product, have more severe ocular problems including anterior segment abnormality, as well as dysmorphic facial features and mental retardation. This suggests there is aberrant expression of a gene at or near the breakpoint in anterior segment and lens development in this family.

Family 2: Individuals in three generations with congenital cataract and renal anomalies have a balanced translocation. Breakpoint identification is proceeding in order to pinpoint a gene whose functional disturbance leads to abnormalities in lens and kidney development.

Family 3: An individual with an apparently balanced, de-novo translocation, has bilateral anterior segment dysgenesis and microphthalmia, suggesting the localisation of a gene important in ocular development.

Conclusion: Many genes underlying hereditary cataract and anterior segment dysgenesis remain unidentified. Chromosomal rearrangements in families with these ocular features can provide a pointer to the underlying genetic cause. Ocular and genetic clinical assessment allows selection of those where molecular analysis is most likely to lead to the identification of candidate lens and anterior segment developmental genes.