CONGENITAL ANTITHROMBIN-III DEFICIENCY (AT-III KYOTO) - IDENTIFICATION OF A POINT MUTATION ALTERING ARGININE-406 TO METHIONINE BEHIND THE REACTIVE SITE

A Japanese patient with congenital antithrombin III (AT-III) deficiency, named AT-III Kyoto, is associated with reduced levels (60% of normal) of AT-III antigen, progressive activity and heparin cofactor activity. The antithrombin III gene of this patient was investigated by polymerase chain reaction (PCR) method followed by direct DNA sequencing analysis, which revealed a G to T transitional mutation resulting in the conversion of arginine-406 to methionine in exon 6. Arginine-406 is located at the 12th amino acid residue from the reactive site on the C-terminal side of AT-III in a core region of the molecule which has been highly conserved during evolution of serine protease inhibitor (serpin) family. It is concluded that AT-III Kyoto is a newly described mutation which is similar to AT-III Utah and lends support to the idea that the conserved region near the reactive site is important in maintaining biological function of the AT-III molecule.