Oculoleptomeningeal amyloidosis associated with a new transthyretin variant Ser64

Arch Neurol. 1999 Sep;56(9):1152-5. doi: 10.1001/archneur.56.9.1152.


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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amyloidosis / diagnosis
  • Amyloidosis / genetics*
  • Amyloidosis / metabolism
  • Autoradiography
  • Central Nervous System Diseases / genetics
  • Cytosine / chemistry
  • Genetic Predisposition to Disease
  • Humans
  • Meninges / metabolism*
  • Mutation*
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / metabolism
  • Oculomotor Nerve / metabolism*
  • Pedigree
  • Peripheral Nervous System Diseases / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Prealbumin / genetics*
  • Sequence Analysis, DNA
  • Thymine / chemistry


  • Prealbumin
  • Cytosine
  • Thymine