EPOS

European Paediatric Ophthalmological Society

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12 Mutation screening of tyrosinase and P-gene in occulocutaneous and ocular albinism

Forster, H., Gonser, M., Lorenz, B., Preising, M.N.
Dept. of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics, University of Regensburg, Germany

Purpose:

To identify mutations in the tyrosinase and P-genes in patients with clinical signs of oculocutaneous or ocular albinism.

Material and Methods:

78 index cases mostly identified by nystagmus, and who presented clinical signs of oculocutaneous (50 cases), ocular albinism (25 cases, 16 males, 4 of these were included in this screen), or nystagmus/macular hypoplasia (3 cases, 1 male) were collected. DNA was extracted. All exons of the tyrosinase and P-genes were amplified by PCR and subjected to SSCP analysis. PCR products showing aberrant banding patterns in SSCP were directly sequenced by dye chain termination method. Mutations were confirmed, when possible, by restriction enzyme digest.

Results:

Actually, about 75% of the analysis is completed.

So far, we have found 10 mutations in the tyrosinase gene. All of these have not been described before. Five of these are possible disease causing mutations (R239T, Q68K, D125G, S229P, V377A). Five are polymorphisms (P38P, L60L, IVS3-3insC, A471A, A482A). With the exception of R239T which was present in the homozygous state all disease causing mutations were identified in the single heterozygous state in 5 patients affected with OCA1,.

In the P-gene we have identified 19 mutations including 8 novel polymorphisms (IVS1+31cc/aa, IVS1+42a/g, IVS10+6c/t, IVS15+78t/c, IVS16-47g/a, IVS22+18g/a, IVS22+25c/g, V459V). In addition, 6 previously reported polymorphisms (IVS11-4a/g, IVS13+26a/g, D257A, R305W, A355A, R419Q, C517C, G780G, S788S) were found.

Two disease causing mutations in the P-gene were identified in index

Conclusion:

Patients diagnosed with ocular or oculocutaneous albinism were shown to carry many different polymorphisms especially in the P-gene. It is well known that the P-gene harbours many polymorphic sequence variations.

We found disease causing mutations in 9 of 66 patients with ocular or oculocutaneous albinism. Five mutations were identified in the tyrosinase gene and 4 mutations in the P-gene. Most of the patients carrying disease causing mutations were single heterozygous for these mutations or compound heterozygous with one of the P-gene polymorphisms. Since we have not already completed our screen further mutations may be expected to complete the compound heterozygous state in these patients.