Oculoleptomeningeal amyloidosis associated with a new transthyretin variant Ser64.
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.


CONCLUSIONS
In this kindred, oculoleptomeningeal amyloidosis is related to a mutation in transthyretin (Phe64Ser).
Uemichi
T
T
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251, USA.
Uitti
R J
RJ
Koeppen
A H
AH
Donat
J R
JR
Benson
M D
MD
D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001345:Autoradiography; D002493:Central Nervous System Diseases / Q000235:genetics; D003596:Cytosine / Q000737:chemistry; D020022:Genetic Predisposition to Disease; D006801:Humans; D008578:Meninges / Q000378:metabolism*; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics* / Q000378:metabolism; D009802:Oculomotor Nerve / Q000378:metabolism*; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011228:Prealbumin / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013941:Thymine / Q000737:chemistry
D011228:Prealbumin; D003596:Cytosine; D013941:Thymine