A new transthyretin mutation associated with amyloidotic vitreous opacities. Asparagine for isoleucine at position 84.
An inherited type of amyloidosis was suspected in an individual of Italian descent who presented with vitreous opacities. Although no family history of amyloidosis was apparent, the patient's transthyretin gene was examined and found not to possess any of the known transthyretin mutations. Complete DNA sequencing revealed a substitution of adenine for thymine in the second base of codon 84 causing an amino acid change of asparagine for isoleucine. The mutation was confirmed by demonstrating the loss of an Sfa N1 restriction endonuclease site. Allele-specific DNA amplification by polymerase chain reaction also was used to confirm the mutation. Either of these tests can be used for diagnosis. Asparagine 84 represents the second mutation associated with amyloidosis to occur at codon 84.
Skinner
M
M
Arthritis Center, Boston University School of Medicine, MA 02118.
Harding
J
J
Skare
I
I
Jones
L A
LA
Cohen
A S
AS
Milunsky
A
A
Skare
J
J
D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis / Q000235:genetics*; D001216:Asparagine / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005128:Eye Diseases / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011228:Prealbumin / Q000235:genetics*; D014822:Vitreous Body
D011228:Prealbumin; D007532:Isoleucine; D001216:Asparagine