A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient "SKO" with familial amyloidotic polyneuropathy.
Transthyretin (TTR) isolated from amyloid fibrils from an Israeli patient ("SKO") with familial amyloidotic polyneuropathy has been studied by two groups of investigators. Originally, a position 49 Thr-->Gly substitution was reported; subsequently, a position 33 Phe-->Ile substitution was found instead. We have studied DNA from this patient by single strand conformation polymorphism analysis, restriction analysis, and DNA sequencing. On one allele, exon 2 contained both a T-->A transversion at the first position of codon 33, encoding the previously described Phe-->Ile substitution, and a G-->A transition at the first position of codon 6, encoding a Gly-->Ser substitution. The originally reported position 49 mutation was not encoded in the genomic DNA. This is the first report of a TTR double-variant allele in a patient with TTR amyloidosis.
Research Service, New York V.A. Medical Center, New York 10010.
D R
DR
Jacobson
J N
JN
Buxbaum
D000483:Alleles; D000595:Amino Acid Sequence; D017772:Amyloid Neuropathies / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D005091:Exons; D006801:Humans; D007438:Introns; D007532:Isoleucine; D007557:Israel; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011228:Prealbumin / Q000235:genetics*; D015183:Restriction Mapping; D012694:Serine
D017931:DNA Primers; D011228:Prealbumin; D007532:Isoleucine; D012694:Serine; D004247:DNA