A basic transthyretin variant (Glu61-->Lys) causes familial amyloidotic polyneuropathy: protein and DNA sequencing and PCR-induced mutation restriction analysis.
A new mutation of transthyretin (TTR) has been identified in a patient with late-onset familial amyloidotic polyneuropathy (FAP) of Japanese origin. Peptide mapping by reverse-phase high performance liquid chromatography to compare the patient's TTR with normal TTR showed the presence of an abnormal peptide. Amino acid sequence analysis of the peptide (residues 49-61) showed a lysine-for-glutamic acid substitution at position 61. This substitution, verified by direct DNA sequencing, was the result of a guanine to adenine change on exon 3 of the TTR gene. A polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA) system was established to rapidly detect the missense mutation. TTR-Lys61 is the first variant TTR with a replacement of the acidic with basic amino acid to be found in the amyloid precursor proteins of FAP.
Shiomi
K
K
Third Department of Medicine, Miyazaki Medical College, Japan.
Nakazato
M
M
Matsukura
S
S
Ohnishi
A
A
Hatanaka
H
H
Tsuji
S
S
Murai
Y
Y
Kojima
M
M
Kangawa
K
K
Matsuo
H
H
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D044466:Asian People; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010449:Peptide Mapping; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D011228:Prealbumin; D011498:Protein Precursors