Oculoleptomeningeal amyloidosis associated with a new transthyretin variant Ser64.

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. To determine if oculoleptomeningeal amyloidosis is caused by a mutation in transthyretin (prealbumin). 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. 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. In this kindred, oculoleptomeningeal amyloidosis is related to a mutation in transthyretin (Phe64Ser).