Background: A Canadian family with oculoleptomeningeal amyloidosis with both central and peripheral nervous system disorders was described in 1988. Death of affected family members resulted from recurrent cerebral hemorrhage.
Objective: To determine if oculoleptomeningeal amyloidosis is caused by a mutation in transthyretin (prealbumin).
Methods: DNA isolated from peripheral blood and archival tissues of affected members of the kindred was studied by direct DNA sequencing and restriction fragment length polymorphism analysis.
Results: Direct DNA sequencing identified a thymine-to-cytosine transition at the second base of codon 64, which resulted in a replacement of serine for phenylalanine. This mutation, which creates an additional HinfI site was detected by restriction fragment length polymorphism analysis in each affected individual.
Conclusion: In this kindred, oculoleptomeningeal amyloidosis is related to a mutation in transthyretin (Phe64Ser).