A lower molecular weight gamma-chain variant in a congenital abnormal fibrinogen (Kyoto)

A gamma-chain variant with a lower molecular weight than the normal gamma chain was detected in a new congenital abnormal fibrinogenwith impaired polymerization of the fibrinmonomer and with normal release of fibrinopeptides A and B in a 45-year-old male. Purified fibrinogenanalyzed on SDS-polyacrylamide gel electrophoresis under the reduced condition contained an abnormal protein band with an apparent molecular weight of 48,000 compared with the gamma chain with a molecular weight of 50,000. This abnormal protein band was found to be a gamma-chain variant from the molar ratio of A alpha chain:B beta chain:gamma chain:abnormal protein (about 2:2:1:1), with positive staining for carbohydrate and crosslinking ability. Crosslinked fibrincontained three types of gamma-gamma dimers with apparent molecular weights of 94,000 (the same as normal major gamma-gamma dimer), 92,000 and 90,000, and the plasmic digests of crosslinked fibrinin the presence of calcium retained three types of gamma-gamma dimer remnants. This suggests that the abnormal gamma-chain variant has a shorter polypeptide chain not in the NH2-terminal but in the COOH-terminal portion, probably at or near the polymerization site. This patient's two daughters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogenwas designated as fibrinogenKyoto, and the gamma- chain variant as gamma Kyoto.