Oculoleptomeningeal amyloidosis associated with a new transthyretin variant Ser64

Background: A Canadian family with oculoleptomeningeal amyloidosis with bot h central and peripheral nervous system disorders was described in 1988. De ath of affected family members resulted from recurrent cerebral hemorrhage. Objective: To determine if oculoleptomeningeal amyloidosis is caused by a m utation in transthyretin (prealbumin). Methods: DNA isolated from peripheral blood and archival tissues of affecte d members of the kindred was studied by direct DNA sequencing and restricti on 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 f or phenylalanine. This mutation, which creates an additional HinfI site was detected by restriction fragment length polymorphism analysis in each affe cted individual. Conclusion: In this kindred, oculoleptomeningeal amyloidosis is related to a mutation in transthyretin (Phe64Ser).