Two new nonsense mutations in type Ia antithrombin III deficiency at Leu 140 and Arg 197.
Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, the molecular basis of hereditary type Ia antithrombin III (AT III) deficiency was disclosed in two families. One mutation was a change from T to A in the codon of TTA for Leu 140 forming a stop codon of TAA, which was confirmed by mutated primer-mediated PCR-HindIII digestion. The application of this method demonstrated that all four affected members had the mutant allele in a heterozygous state and that none of unaffected subjects had this mutation. Another mutation in the second family was a change from C to T in the codon of CGA for Arg 197 also forming a stop codon of TGA, which was confirmed by PCR-HaeIII digestion. Based on these, it was concluded that the two new nonsense mutations in the AT III gene in a heterozygous state are the molecular basis of hereditary type Ia AT III deficiency.
First Department of Internal Medicine, University of Tokushima, Japan.
A
A
Tomonari
H
H
Iwahana
K
K
Yoshimoto
T
T
Shigekiyo
S
S
Saito
M
M
Itakura
D000990:Antithrombin III / Q000235:genetics; D020152:Antithrombin III Deficiency; D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D005799:Genes, Dominant / Q000235:genetics*; D007122:Immunoelectrophoresis; D007930:Leucine / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
C094963:antithrombin III Arg197STOP; D000990:Antithrombin III; D001120:Arginine; D007930:Leucine